About MBD4
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
MBD4 c.817G>A, p.(Ala273Thr)
Classification
Benign
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is benign. Select a step to read what it means.
Benign.A benign classification under the recorded framework.
In plain language
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.
LYFE Sciences is an AI system, and it can make mistakes.
Criteria may be applied incorrectly, sources may be misread, and a
confident-looking classification can still be wrong.
Double-check every criterion and its underlying evidence
before relying on any call.
01The reasoning
How it was classified
The recorded framework is Not recorded. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
Recorded applied criteria
The applied criteria and their strengths are shown as assessed under the stated framework.
Pathogenic evidence criteria: 0
Benign evidence criteria: 4
Pathogenic criteria applied · 0
No pathogenic criterion marked as applied in the recorded assessment.
Benign criteria applied · 4
BA1Stand alone
BA1 · stand alone
This variant is present at extremely high allele frequency in population databases, far exceeding the BA1 threshold of >1%. gnomAD v2.1: AF=7.89% (22,303/282,770 alleles, 999 homozygotes). gnomAD v4.1: AF=8.41% (135,695/1,614,010 alleles, 6,177 homozygotes). Highest subpopulation frequency in Ashkenazi Jewish: 16.24% (v2.1) / 16.28% (v4.1). The presence of 999–6,177 homozygotes across gnomAD datasets definitively establishes this as a common benign polymorphism.
BS1Strong
BS1 · strong
Allele frequency far exceeds the BS1 threshold of >0.3%. gnomAD v2.1 AF=7.89% and gnomAD v4.1 AF=8.41% both vastly surpass the 0.3% cutoff. While BA1 (stand-alone benign) supersedes this criterion, the population data independently satisfies BS1 at strong benign strength.
BS2Strong
BS2 · strong
Observed in 999 homozygous individuals in gnomAD v2.1 and 6,177 homozygous individuals in gnomAD v4.1, definitively confirming observation in healthy adults. For MBD4-associated cancer predisposition syndromes (colorectal oligopolyposis, melanoma), this number of homozygotes is incompatible with a highly penetrant pathogenic role.
BP4Supporting
BP4 · supporting
Multiple lines of computational evidence suggest no impact on gene product. REVEL score is 0.212 (well below the 0.5 pathogenicity threshold), and BayesDel score is -0.418 (negative, predicting benign). SpliceAI identifies no splicing impact. No HCI prior probability score is available for MBD4.
Recorded classification: Benign
gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: BA1 stand-alone benign, BS1 strong benign, BS2 strong benign, BP4 supporting benign; combination = 1 stand-alone benign + 2 strong benign + 1 supporting benign, which maps to Benign.
02The sources
Evidence at a glance
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1
gnomAD v2.1
Population frequency
135,695 / 1,614,010 alleles
gnomAD v4.1: 135,695 / 1,614,010 alleles. Recorded AF 0.0840732. Recorded homozygote count 6177.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.0788733; MAF= 7.88733%, 22303/282770 alleles, homozygotes = 999) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.162423; MAF= 16.24228%, 1684/10368 alleles, homozygotes = 131); grpmax FAF= 0.106406.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.09180238870792616, 1691/18420 alleles, homozygotes = 90).
No screenshot for this evidence
Computational predictions
Not recorded
No SpliceAI or REVEL score is recorded in the fields used for this tile.
ClinVar submissions
Not recorded
A ClinVar laboratory submission summary was not recorded. ClinVar API review status: criteria provided, multiple submitters, no conflicts.
Context only
ClinVar ↗
Functional evidence
Statement recorded
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. MBD4, a DNA glycosylase, is infrequently altered in cancer.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
15 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV51444644, n = 15 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under Not recorded, with the data and sources behind each one.
26 criteria with recorded statuses: 4 met · 17 not met · 0 not assessed · 5 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_001276270.2:c.817G>A (p.Ala273Thr) in MBD4 is a common polymorphism present at 7.89–8.41% allele frequency across gnomAD datasets with 999–6,177 homozygous individuals, far exceeding the BA1 stand-alone benign threshold of >1%.
The variant is classified as Benign in ClinVar (Variation ID 1236752) with 2-star review status and five clinical laboratory submissions unanimously agreeing on a benign classification, consistent with the population frequency data.
Multiple in silico predictors support a benign effect: REVEL score 0.212 and BayesDel score -0.418, with no evidence of splicing impact from SpliceAI.
No pathogenic evidence was identified: PVS1 is not applicable to this missense variant; no functional studies (PS3), de novo events (PS2/PM6), segregation data (PP1), or case-control enrichment (PS4) were found.
Based on BA1 alone, this variant meets stand-alone benign criteria. Additional benign evidence from BS1, BS2, and BP4 further supports a benign classification. Classification: BENIGN.
No criteria match.
Met · 4
BA1 Stand aloneThis variant is present at extremely high allele frequency in population databases, far exceeding the BA1 threshold of >1%. gnomAD v2.1: AF=7.89% (22,303/282,770 alleles, 999 homozygotes). gnomAD v4.1: AF=8.41% (135,695/1,614,010 alleles, 6,177 homozygotes). Highest subpopulation frequency in Ashkenazi Jewish: 16.24% (v2.1) / 16.28% (v4.1). The presence of 999–6,177 homozygotes across gnomAD datasets definitively establishes this as a common benign polymorphism. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: AF=7.89%
- 22
- 303/282
- 770 alleles
- 999 homozygotes
- grpmax FAF=10.64%
- gnomAD v4.1: AF=8.41%
- 135
- 695/1
- 614
- 010 alleles
- 6
- 177 homozygotes
- grpmax FAF=11.67%
- Ashkenazi Jewish subpopulation: AF=16.24% (v2.1) / 16.28% (v4.1)
- All population frequencies far exceed BA1 >1% threshold
Sources
BS1 StrongAllele frequency far exceeds the BS1 threshold of >0.3%. gnomAD v2.1 AF=7.89% and gnomAD v4.1 AF=8.41% both vastly surpass the 0.3% cutoff. While BA1 (stand-alone benign) supersedes this criterion, the population data independently satisfies BS1 at strong benign strength. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: AF=7.89% >> 0.3% threshold
- gnomAD v4.1: AF=8.41% >> 0.3% threshold
Sources
BS2 StrongObserved in 999 homozygous individuals in gnomAD v2.1 and 6,177 homozygous individuals in gnomAD v4.1, definitively confirming observation in healthy adults. For MBD4-associated cancer predisposition syndromes (colorectal oligopolyposis, melanoma), this number of homozygotes is incompatible with a highly penetrant pathogenic role. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: 999 homozygotes
- gnomAD v4.1: 6
- 177 homozygotes
- Numbers incompatible with highly penetrant disease causation
Sources
BP4 SupportingMultiple lines of computational evidence suggest no impact on gene product. REVEL score is 0.212 (well below the 0.5 pathogenicity threshold), and BayesDel score is -0.418 (negative, predicting benign). SpliceAI identifies no splicing impact. No HCI prior probability score is available for MBD4. Details ▾Hide ▴
Evidence considered
- REVEL: 0.212 (below 0.5
- predicts benign)
- BayesDel: -0.418 (negative
- SpliceAI: no prediction (no splicing impact detected)
Sources
Not met · 17 · evaluated, threshold not reached
PS2 No de novo data available for NM_001276270.2:c.817G>A. No literature or database reports of a confirmed de novo occurrence were identified. Details ▾Hide ▴
Evidence considered
- No de novo reports found in ClinVar submissions
- literature
- or databases.
Still missing
- No parental testing data available.
PS3 No well-established functional studies directly testing NM_001276270.2:c.817G>A (p.Ala273Thr) or a systematically characterized range including this residue were identified. OncoKB reports 'Unknown Oncogenic Effect' with no variant-specific functional PMIDs. The domain-level mechanism data for MBD4 loss of function applies to truncating variants, not this missense substitution. Details ▾Hide ▴
Evidence considered
- OncoKB reports Unknown Oncogenic Effect
- no variant-specific functional studies identified. MBD4 LOF mechanism literature (PMID:31322271
- PMID:35460607) describes truncating variants
- not missense at residue 273.
Still missing
- No experimental functional data for p.Ala273Thr.
Sources
PS4 No case-control or cohort data demonstrating statistically significant enrichment of NM_001276270.2:c.817G>A in affected individuals compared to population controls. The variant is highly prevalent in the general population (AF 7.89%), making any case-control enrichment unlikely. Details ▾Hide ▴
Evidence considered
- No case-control data available. Population frequency of 7.89% precludes a pathogenic enrichment argument.
Still missing
- No affected vs. control comparison data.
Sources
PM1 Residue 273 is not located in a statistically significant mutational hotspot (cancerhotspots.org negative). No domain-level evidence was identified demonstrating that missense substitutions in the region of residue 273 disrupt a critical functional domain in a manner established for disease causation. Details ▾Hide ▴
Evidence considered
- Cancerhotspots.org: residue not significant
- exact variant not listed. No domain-specific functional characterization for the region around residue 273.
Still missing
- No domain-level functional mapping for Al273 region.
PM2 This variant is common in population databases. gnomAD v2.1: AF=7.89% (22,303/282,770 alleles, 999 homozygotes); gnomAD v4.1: AF=8.41% (135,695/1,614,010 alleles, 6,177 homozygotes). Far exceeds the PM2 threshold of <0.1% absent/rare. Details ▾Hide ▴
Evidence considered
- Population frequency 7.89% in gnomAD v2.1 and 8.41% in v4.1 — common variant
- not absent/rare.
Sources
PM6 No confirmed de novo occurrence of NM_001276270.2:c.817G>A has been reported. No literature or database entries document a de novo event with confirmed maternity and paternity. Details ▾Hide ▴
Evidence considered
- No de novo reports found.
Still missing
- No parental testing data available.
PP1 No cosegregation data are available for NM_001276270.2:c.817G>A. No family studies demonstrating segregation with disease have been reported. Details ▾Hide ▴
Evidence considered
- No segregation studies found.
Still missing
- No family-based segregation analysis.
PP2 MBD4 is not established as a gene with a low rate of benign missense variation and a high rate of pathogenic missense variants. Additionally, the high population frequency of p.Ala273Thr (AF 7.89%) suggests this is a common benign missense variant. Details ▾Hide ▴
Evidence considered
- MBD4 does not meet PP2 gene-level criteria. p.Ala273Thr is a common missense variant in the general population.
Sources
PP3 Multiple in silico predictors indicate a benign effect. REVEL score is 0.212 (below the 0.5 pathogenicity threshold) and BayesDel score is -0.418 (negative, predicting benign). No SpliceAI prediction is available, but there is no evidence of splicing impact. Details ▾Hide ▴
Evidence considered
- REVEL: 0.212 (benign-leaning). BayesDel: -0.418 (benign). SpliceAI: no prediction (no splicing impact detected).
Sources
PP4 No patient-specific phenotype data are available for this case. There is no evidence that the patient's phenotype is highly specific for MBD4-related disease. Details ▾Hide ▴
Evidence considered
- No patient phenotype data provided.
Still missing
- No clinical phenotype information for the proband.
PP5 ClinVar classification for Variation ID 1236752 is Benign (not Pathogenic) with review status 'criteria provided, multiple submitters, no conflicts' (2-star). All six submitters classify as Benign. PP5 requires a reputable source reporting the variant as pathogenic; ClinVar consensus is Benign. Details ▾Hide ▴
Evidence considered
- ClinVar Variation ID 1236752: Benign classification
- 6 submitters
- 5 clinical labs. Review status: 2-star (not 3-star expert panel). No submitter classifies as Pathogenic.
Sources
BS3 No well-established in vitro or in vivo functional studies have been performed on NM_001276270.2:c.817G>A (p.Ala273Thr) demonstrating no damaging effect on protein function or splicing. In silico predictions alone (REVEL, BayesDel) support BP4, not BS3. Details ▾Hide ▴
Evidence considered
- No functional studies identified for this variant.
Still missing
- No experimental functional data for p.Ala273Thr.
BS4 No segregation data or family studies are available to assess whether this variant fails to segregate with disease in affected families. Details ▾Hide ▴
Evidence considered
- No segregation studies found.
Still missing
- No family-based cosegregation analysis.
BP1 MBD4 is not established as a gene in which only truncating variants cause disease. While loss-of-function variants are reported in association with MBD4-related tumor predisposition (PMID:31322271, PMID:35460607), it has not been demonstrated that missense variants at this gene cannot be pathogenic. BP1 cannot be applied. Details ▾Hide ▴
Evidence considered
- MBD4 LOF mechanism supported but gene not established as exclusively truncating-variant-driven. Missense pathogenicity cannot be excluded at the gene level.
Sources
pvs1_gene_context
BP2 No evidence of this variant observed in trans with a known pathogenic MBD4 variant. No data from recessive disease contexts are available. Details ▾Hide ▴
Evidence considered
- No trans-phase observations available.
Still missing
- No phasing data with pathogenic variants.
BP5 No evidence that this variant has been observed in a case with an alternative molecular basis for disease. No patient-level data are available for evaluation. Details ▾Hide ▴
Evidence considered
- No case-level molecular data available.
Still missing
- No patient-specific molecular workup data.
BP6 ClinVar Variation ID 1236752 is classified as Benign with review status 'criteria provided, multiple submitters, no conflicts' (2-star). The PP5/BP6 rule requires ClinVar 3-star expert panel status to automatically apply at supporting strength. Five clinical laboratories independently classify as Benign (GeneDx, Ambry Genetics, ARUP Laboratories, Labcorp/Invitae, Myriad Genetics), which is consistent with the BA1/BS1/BS2/BP4 evidence but does not independently meet the 3-star threshold for BP6 application under the current framework. Details ▾Hide ▴
Evidence considered
- ClinVar Variation ID 1236752: Benign
- 2-star review status
- 5 clinical labs classify as Benign
- 1 non-clinical submitter also Benign
- Does not meet 3-star expert panel threshold for automatic BP6 application
Still missing
- ClinVar review status is 2-star
- not 3-star
- BP6 supporting threshold not met per framework rules despite strong clinical consensus.
Sources
Not applicable · 5· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_001276270.2:c.817G>A is a missense variant (p.Ala273Thr) and does not fall into the default generic PVS1 null-variant buckets of nonsense, frameshift, or canonical ±1,2 splice consensus variants. Details ▾Hide ▴
Evidence considered
- Missense substitution
- PVS1 decision tree does not apply to missense variants.
Sources
pvs1_variant_assessment
PS1 N/ANo same-residue comparator variant with a pathogenic classification was identified; the variant is a novel amino acid change (Ala273Thr) with no known pathogenic variant at this position. Details ▾Hide ▴
Evidence considered
- No pathogenic variant with the same amino acid change identified.
PM5 N/AUnable to confirm classic same-residue PM5 semantics; no comparator pathogenic missense variants at the same codon (Ala273) were identified in ClinVar. The PM5 candidate harvesting returned no eligible comparators. Details ▾Hide ▴
Evidence considered
- No same-residue pathogenic comparator variants identified in ClinVar.
Sources
pm5_candidates
BP7 N/ANM_001276270.2:c.817G>A is a missense variant (p.Ala273Thr), not a synonymous/silent variant. BP7 applies only to synonymous variants with no predicted splicing impact. Details ▾Hide ▴
Evidence considered
- Missense variant
- BP7 is reserved for synonymous variants.
PS5 N/APS5 is not a standard ACMG/AMP 2015 criterion and no equivalent PS5 rule is defined in the generic_acmg framework. Details ▾Hide ▴
No further detail was recorded.
Identifiers
- Gene
- MBD4
- Transcript
- NM_001276270.2
- Coding (HGVS c.)
- NM_001276270.2:c.817G>A
- Protein (HGVS p.)
- NP_001263199.1:p.(Ala273Thr)
- GRCh38
- chr3:129436827 C>T
- GRCh37
- chr3:129155670 C>T
- ClinVar
- 1236752
- COSMIC
- COSV51444644
Gene diagram
Every interpreted variant in MBD4, mapped onto the exon structure of NM_001276270.2. Select a row to find it on the plot.
MBD4NM_001276270.2
Fetching transcript structure from UCSC…
Exons
—
Transcript span
—
Strand
—
Variants mapped
—
Source
UCSC ncbiRefSeqCurated
All variants in MBD4
—
Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
135,695 / 1,614,010 alleles
AF 0.0841 · 6177 homozygotes · FAF 0.117
gnomAD v2.1
22,303 / 282,770 alleles
AF 0.0789 · 999 homozygotes · FAF 0.106
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 0.084 · 135695 / 1,614,010 alleles · 6177 hom · FAF 0.12
| Ashkenazi Jewish4821 / 29,606 | 0.16404 hom |
| Middle Eastern752 / 6,062 | 0.1265 hom |
| South Asian10157 / 91,076 | 0.11674 hom |
| Remaining individuals5804 / 62,506 | 0.093293 hom |
| European (non-Finnish)100487 / 1,179,954 | 0.0854268 hom |
| African/African American5098 / 75,032 | 0.068180 hom |
| Admixed American3788 / 60,020 | 0.063149 hom |
| East Asian2278 / 44,880 | 0.05181 hom |
| European (Finnish)2482 / 63,962 | 0.03962 hom |
| Amish28 / 912 | 0.0311 hom |
gnomAD v2.1
AF 0.079 · 22303 / 282,770 alleles · 999 hom · FAF 0.11
| Ashkenazi Jewish1684 / 10,368 | 0.16131 hom |
| South Asian3352 / 30,612 | 0.11207 hom |
| Remaining individuals686 / 7,224 | 0.09538 hom |
| European (non-Finnish)10731 / 129,128 | 0.083434 hom |
| African/African American1720 / 24,960 | 0.06962 hom |
| East Asian1213 / 19,948 | 0.06140 hom |
| Admixed American1984 / 35,436 | 0.05665 hom |
| European (Finnish)933 / 25,094 | 0.03722 hom |
gnomAD-Canada
AF not recorded · ? / ? alleles
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0.0840732; MAF= 8.40732%, 135695/1614010 alleles, homozygotes = 6177) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.162839; MAF= 16.28386%, 4821/29606 alleles, homozygotes = 404); grpmax FAF= 0.116705.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.0788733; MAF= 7.88733%, 22303/282770 alleles, homozygotes = 999) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.162423; MAF= 16.24228%, 1684/10368 alleles, homozygotes = 131); grpmax FAF= 0.106406.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.09180238870792616, 1691/18420 alleles, homozygotes = 90).
Other predictors
- REVEL
- 0.212
- BayesDel
- -0.418
How the predictions were used
BP4 SupportingMultiple lines of computational evidence suggest no impact on gene product. REVEL score is 0.212 (well below the 0.5 pathogenicity threshold), and BayesDel score is -0.418 (negative, predicting benign). SpliceAI identifies no splicing impact. No HCI prior probability score is available for MBD4. Details ▾Hide ▴
Evidence considered
- REVEL: 0.212 (below 0.5
- predicts benign)
- BayesDel: -0.418 (negative
- SpliceAI: no prediction (no splicing impact detected)
Sources
PP3 Multiple in silico predictors indicate a benign effect. REVEL score is 0.212 (below the 0.5 pathogenicity threshold) and BayesDel score is -0.418 (negative, predicting benign). No SpliceAI prediction is available, but there is no evidence of splicing impact. Details ▾Hide ▴
Evidence considered
- REVEL: 0.212 (benign-leaning). BayesDel: -0.418 (benign). SpliceAI: no prediction (no splicing impact detected).
Sources
BP7 N/ANM_001276270.2:c.817G>A is a missense variant (p.Ala273Thr), not a synonymous/silent variant. BP7 applies only to synonymous variants with no predicted splicing impact. Details ▾Hide ▴
Evidence considered
- Missense variant
- BP7 is reserved for synonymous variants.
Statement
In silico
REVEL score = 0.212. BayesDel score = -0.417963.
7 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata. None of the listed paper records explicitly indicates that the variant is named.
Recorded publications
-
PMID 23619275 ↗ACMG position statement on prenatal/preconception expanded carrier screening.ACMG position statement on prenatal/preconception expanded carrier screening. Discusses general carrier screening policy and does not mention MBD4 or NM_001276270.2:c.817G>A.Does not name this variant
-
PMID 25730230 ↗Expanded carrier screening in reproductive medicine-points to consider: a joint statement of the American College of Medical Genetics and Genomics, American College of Obstetricians and Gynecologists, National Society of Genetic Counselors, Perinatal Quality Foundation, and Society for Maternal-Fetal Medicine.Joint statement on expanded carrier screening in reproductive medicine from ACMG, ACOG, NSGC, Perinatal Quality Foundation, and SMFM. Discusses carrier screening panel criteria and does not mention MBD4 or NM_001276270.2:c.817G>A.Does not name this variant
-
PMID 25741868 ↗Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.ACMG/AMP standards and guidelines for the interpretation of sequence variants. Foundational methods paper defining the variant classification framework. Does not mention MBD4 or NM_001276270.2:c.817G>A.Does not name this variant
-
PMID 23169492 ↗The perspective from EASAC and FEAM on direct-to-consumer genetic testing for health-related purposes.Fears R et al. · 2013EASAC and FEAM perspective on direct-to-consumer genetic testing for health-related purposes. Policy paper discussing regulation of DTC genetic testing services. Does not mention MBD4 or NM_001276270.2:c.817G>A.Does not name this variant
-
PMID 22947299 ↗Specific guidelines for assessing and improving the methodological quality of economic evaluations of newborn screening.Langer A et al. · 2012Specific guidelines for assessing and improving the methodological quality of economic evaluations of newborn screening. Does not mention MBD4 or NM_001276270.2:c.817G>A.Does not name this variant
-
PMID 23037933 ↗Including the initial newborn screening bloodspot collection device serial number on birth certificates: basis and recommendations from the Secretary of Health and Human Services' Advisory Committee on Heritable Disorders in Newborns and Children.Therrell BL et al. · 2013Basis and recommendations for including newborn screening bloodspot collection device serial numbers on birth certificates. Does not mention MBD4 or NM_001276270.2:c.817G>A.Does not name this variant
-
PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Methods paper describing an evidence-based classification system. Does not mention MBD4 or NM_001276270.2:c.817G>A.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
135,695 / 1,614,010 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Captured SpliceAI source record
Open source ↗
ClinVar
Captured ClinVar source record
Open source ↗
COSMIC
Captured COSMIC source record
Open source ↗
Cancer hotspots
Captured Cancer Hotspots source record
Open source ↗
OncoKB
Captured OncoKB source record
Open source ↗
All source links
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/1236752/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/3-129155670-C-T?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr3-129436827-C-T?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/3-129436827-C-T
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_001276270.2%3Ac.8…
- OncoKB ↗www.oncokb.org/gene/MBD4/A273T
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=122997726
- Cancer hotspots ↗www.cancerhotspots.org/
Statements for reports
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0.0840732; MAF= 8.40732%, 135695/1614010 alleles, homozygotes = 6177) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.162839; MAF= 16.28386%, 4821/29606 alleles, homozygotes = 404); grpmax FAF= 0.116705.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.0788733; MAF= 7.88733%, 22303/282770 alleles, homozygotes = 999) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.162423; MAF= 16.24228%, 1684/10368 alleles, homozygotes = 131); grpmax FAF= 0.106406.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.09180238870792616, 1691/18420 alleles, homozygotes = 90).
ClinVar
This variant is present in ClinVar (Variation ID: 1236752); submission details unavailable.
In silico
REVEL score = 0.212. BayesDel score = -0.417963.
Functional
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. MBD4, a DNA glycosylase, is infrequently altered in cancer.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV51444644, n = 15 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.