About MBD4
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
MBD4 c.1382A>G, p.(Asn461Ser)
Classification
Uncertain significance
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is uncertain. Select a step to read what it means.
Uncertain.The recorded classification is uncertain significance.
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: 1
Pathogenic criteria applied · 0
No pathogenic criterion marked as applied in the recorded assessment.
Benign criteria applied · 1
BP4Supporting
BP4 · supporting
Multiple lines of computational evidence suggest no significant impact on the gene product. BayesDel scores -0.063 (benign) and SpliceAI predicts no splicing impact (max delta = 0.15). While REVEL scores 0.54 (borderline deleterious), the preponderance of in silico tools (2 of 3) supports a benign interpretation.
Recorded classification: Uncertain significance
gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: BP4 supporting; combination = 1 supporting benign, which maps to VUS.
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
3,262 / 1,614,054 alleles
gnomAD v4.1: 3,262 / 1,614,054 alleles. Recorded AF 0.002021. Recorded homozygote count 8.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.0016941; MAF= 0.16941%, 479/282746 alleles, homozygotes = 2) and has highest observed frequency in the European (Finnish) population (AF= 0.00310658; MAF= 0.31066%, 78/25108 alleles, homozygotes = 0); grpmax FAF= 0.0025446.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.001628841350852427, 30/18418 alleles, homozygotes = 0).
No listed criterion applied
SpliceAI score
0.150 maximum delta
Recorded SpliceAI maximum delta score: 0.150. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
7 reported laboratory submissions
4 Likely benign · 2 Uncertain significance · 1 Likely Benign. ClinVar API review status: criteria provided, conflicting classifications.
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
No matching record reported
This variant has not previously been reported in somatic cancers (COSMIC).
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: 1 met · 20 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
MBD4 NM_001276270.2:c.1382A>G (p.Asn461Ser) is a missense variant in exon 5 encoding a non-conservative amino acid substitution from asparagine to serine at codon 461.
This variant is present in gnomAD v4.1 at an allele frequency of 0.202% (3,262/1,614,054 alleles, including 8 homozygotes) and in gnomAD v2.1 at 0.169% (479/282,746 alleles, including 2 homozygotes), indicating it is not a rare variant in the general population.
Multiple lines of in silico evidence suggest no significant impact on the gene product: BayesDel scores -0.063 (benign) and SpliceAI predicts no splicing impact (max delta score 0.15). REVEL scores 0.54 (borderline deleterious) but does not overcome the preponderance of benign computational evidence (BP4 supporting).
No variant-specific functional studies, segregation data, de novo observations, or case-control studies were identified in the literature or ClinVar submissions.
ClinVar classifies this variant as Likely benign based on submissions from multiple clinical laboratories (4 Likely benign, 2 Uncertain significance), though the aggregate review status remains single-submitter level.
Overall, the only criterion met is BP4 at supporting strength. No pathogenic criteria are met. Insufficient evidence exists to classify this variant as either pathogenic or likely pathogenic; the classification is Uncertain Significance (VUS). The population frequency data and clinical laboratory consensus lean toward a benign interpretation but do not meet formal benign classification thresholds.
No criteria match.
Met · 1
BP4 SupportingMultiple lines of computational evidence suggest no significant impact on the gene product. BayesDel scores -0.063 (benign) and SpliceAI predicts no splicing impact (max delta = 0.15). While REVEL scores 0.54 (borderline deleterious), the preponderance of in silico tools (2 of 3) supports a benign interpretation. Details ▾Hide ▴
Evidence considered
- BayesDel = -0.063 (benign)
- SpliceAI max delta = 0.15 (no splice impact). REVEL = 0.54 conflicts but does not override the two benign-supporting tools.
Sources
Not met · 20 · evaluated, threshold not reached
PS1 No alternative nucleotide change at c.1382 has been reported as pathogenic. No evidence that a different amino acid substitution at this position is established as disease-causing. Details ▾Hide ▴
Evidence considered
- ClinVar contains no pathogenic variant at the same nucleotide position (c.1382) with a different alteration.
Still missing
- No systematic search for same-nucleotide pathogenic variants beyond ClinVar.
Sources
PS2 No de novo data are available for this variant. No confirmed de novo observation has been reported in ClinVar submissions or the literature. Details ▾Hide ▴
Evidence considered
- No de novo observations in 8 ClinVar submissions.
Still missing
- No parental testing data available.
Sources
PS3 No variant-specific functional studies were identified. OncoKB reports Unknown Oncogenic Effect. A ClinVar submission (SCV002070998) explicitly notes the absence of functional studies for this variant. A separate submission (SCV004031892) references the variant's presence in uveal melanoma patients but provides no functional assay data. Details ▾Hide ▴
Evidence considered
- OncoKB: no curated functional evidence. ClinVar submissions: no functional data provided. One submitter (SCV002070998) states lack of functional studies explicitly.
Still missing
- No experimental functional characterization of p.Asn461Ser exists in the literature.
Sources
PS4 No case-control or statistical evidence demonstrates enrichment of this variant in affected individuals. No prevalence data comparing affected vs. unaffected populations are available. Details ▾Hide ▴
Evidence considered
- gnomAD provides population frequency but no case-control comparison. ClinVar submissions lack prevalence statistics.
Still missing
- No case-control study data.
Sources
PM1 The variant (p.Asn461Ser) is not located in a statistically significant mutational hotspot (cancerhotspots.org analysis negative) and no well-characterized critical functional domain specific to this residue position was identified. While one ClinVar submission notes the variant is 'located in a domain of the MBD4 protein that is known to be functional,' this is a general domain-level statement without residue-specific functional characterization sufficient for PM1. Details ▾Hide ▴
Evidence considered
- Cancerhotspots.org: residue not significant. ClinVar: generic domain statement without residue-specific characterization.
Still missing
- No residue-specific functional domain characterization for position 461.
Sources
PM2 This variant is present in gnomAD v2.1 at AF = 0.169% (479/282,746 alleles, 2 homozygotes) and in gnomAD v4.1 at AF = 0.202% (3,262/1,614,054 alleles, 8 homozygotes). Both exceed the 0.1% PM2 threshold for a rare variant absent from population databases. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 AF = 0.169%
- gnomAD v4.1 AF = 0.202%. Both exceed the generic ACMG PM2 threshold of <0.1%.
Sources
PP1 No segregation data are available for this variant. No family studies demonstrating cosegregation with disease have been reported. Details ▾Hide ▴
Evidence considered
- ClinVar submissions lack any segregation information. One submission (SCV004031892) notes that familial segregation information was not included in publications referencing this variant.
Still missing
- No family segregation data available.
Sources
PP2 No gene-level constraint metrics (e.g., missense Z-score, missense o/e ratio) were available for MBD4 to establish a low rate of benign missense variation. Without quantitative constraint data, PP2 cannot be applied. Details ▾Hide ▴
Evidence considered
- No MBD4 missense constraint data available in the evidence packet.
Still missing
- Missense constraint scores (Z-score
- o/e) for MBD4 not retrieved.
PP3 In silico predictors are conflicting. REVEL scores 0.54 (deleterious, >0.5 threshold), but BayesDel scores -0.063 (benign, <0 threshold) and SpliceAI predicts no splicing impact (max delta = 0.15). Only one of three computational tools supports a deleterious effect; multiple lines of concordant evidence are required for PP3. Details ▾Hide ▴
Evidence considered
- REVEL = 0.54 (deleterious)
- BayesDel = -0.063 (benign)
- SpliceAI max delta = 0.15 (no splice impact). Conflicting and insufficient for PP3.
Sources
PP5 ClinVar classifies this variant as Likely benign (not Pathogenic) with a review status of 'criteria provided, single submitter' (1-star). PP5 requires a reputable source reporting the variant as pathogenic; a Likely benign classification does not support PP5. Additionally, per memory guidance, PP5 at supporting strength only applies when ClinVar review status is 3-star expert panel, which is not met here. Details ▾Hide ▴
Evidence considered
- ClinVar classification: Likely benign (Variation ID: 1336001)
- review status: 1-star. Does not support PP5.
Sources
BA1 gnomAD v4.1 allele frequency is 0.202% (v2.1: 0.169%), well below the 1% BA1 threshold for a benign common variant. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 AF = 0.169%
- v4.1 AF = 0.202%. Both below 1% BA1 threshold.
Sources
BS1 gnomAD v2.1 AF = 0.169% (grpmax FAF = 0.254%) and v4.1 AF = 0.202% (grpmax FAF = 0.236%). Both overall and population-maximum frequencies are below the 0.3% BS1 threshold for a dominant disorder. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 AF = 0.169%
- grpmax FAF = 0.254%
- v4.1 AF = 0.202%
- grpmax FAF = 0.236%. All below 0.3% BS1 threshold.
Sources
BS2 While gnomAD reports homozygotes for this variant (2 in v2.1, 8 in v4.1), there is no confirmation that these individuals are healthy adults, which is required for BS2. Additionally, MBD4-associated tumor predisposition has variable age of onset and penetrance, making BS2 application from population databases alone inappropriate. Details ▾Hide ▴
Evidence considered
- gnomAD homozygotes: 2 in v2.1
- 8 in v4.1. No confirmed healthy adult status
- MBD4 disorders have variable penetrance.
Still missing
- No clinical confirmation that gnomAD homozygotes are healthy adults without disease.
Sources
BS3 No well-established functional studies demonstrate that this variant has no deleterious effect. No in vitro or in vivo experimental data exist for p.Asn461Ser. Details ▾Hide ▴
BS4 No segregation data are available demonstrating lack of cosegregation with disease. No family studies have been reported for this variant. Details ▾Hide ▴
Evidence considered
- No family segregation data available.
Still missing
- No segregation studies.
BP1 MBD4 is not a gene for which primarily truncating variants are known to cause disease. The PVS1 gene-level analysis identified both truncating (c.217C>T/p.Gln73*) and missense variants in the disease literature. Additionally, this is a missense variant; BP1 specifically applies to missense variants in genes where the primary disease mechanism is through truncation. Details ▾Hide ▴
Evidence considered
- MBD4 disease mechanism involves both LOF and missense variants
- not a truncating-only disease gene.
Sources
pvs1_gene_context
BP2 No data are available demonstrating that this variant has been observed in trans with a pathogenic variant in MBD4 (for a recessive disorder) or in cis with a known pathogenic variant. Details ▾Hide ▴
Evidence considered
- No trans or cis phase data available.
Still missing
- No phase information from clinical testing.
BP5 No case has been reported in which this variant was observed together with an alternate molecular basis for disease in the same individual. No evidence of an explanatory second variant in MBD4 or another gene was identified. Details ▾Hide ▴
Evidence considered
- No alternate molecular explanation documented in any ClinVar submission or publication.
Still missing
- No systematic search for co-occurring pathogenic variants.
BP6 ClinVar review status for Variation ID 1336001 is 'criteria provided, single submitter' (1-star), not 3-star expert panel. Per governing rules, BP6 at supporting strength requires ClinVar 3-star expert panel review. The variant's ClinVar classification (Likely benign) cannot be leveraged for BP6 at this review level. Details ▾Hide ▴
Evidence considered
- ClinVar classification: Likely benign
- review status: 1-star (criteria provided
- single submitter). Does not meet 3-star EP requirement for BP6.
Still missing
- No expert panel review available to support BP6.
Sources
PS5 No evidence that this is a well-established pathogenic variant identified in multiple unrelated affected individuals with the same phenotype. No variant-specific case reports with validated clinical data were identified. Details ▾Hide ▴
Evidence considered
- ClinVar classifications are predominantly Likely benign or Uncertain significance
- not Pathogenic.
Still missing
- No case reports with detailed phenotype for this exact variant.
Sources
Not applicable · 5· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/AThis is a missense variant (c.1382A>G, p.Asn461Ser), not a nonsense, frameshift, or canonical ±1,2 splice-site variant eligible for PVS1 under the ClinGen SVI PVS1 decision framework (PMC6185798). Details ▾Hide ▴
Evidence considered
- Missense variant
- does not fall into default PVS1 null-variant buckets.
Sources
PM5 N/ANo same-residue (p.Asn461) pathogenic comparator variant was identified in ClinVar. The pm5_candidates analysis found zero eligible comparator variants. Details ▾Hide ▴
Evidence considered
- Automated PM5 candidate harvesting found no same-residue pathogenic variants in ClinVar.
Sources
pm5_candidates
PM6 N/ANo de novo observation has been reported for this variant. PM6 requires confirmed de novo status with maternity and paternity confirmed. Details ▾Hide ▴
Evidence considered
- No de novo observations in ClinVar submissions.
Still missing
- No parental testing data.
Sources
PP4 N/ANo patient phenotype or clinical data are available for this variant. PP4 requires the variant to be identified in a patient with a phenotype highly specific for the gene/disease. Details ▾Hide ▴
Evidence considered
- No patient-specific phenotype data in the case folder.
Still missing
- No patient phenotype information.
BP7 N/AThis is a missense variant (c.1382A>G, p.Asn461Ser), not a synonymous (silent) variant. BP7 applies exclusively to synonymous variants with no predicted splice impact. Details ▾Hide ▴
Evidence considered
- Missense variant
- BP7 is specific to synonymous variants.
Identifiers
- Gene
- MBD4
- Transcript
- NM_001276270.2
- Coding (HGVS c.)
- NM_001276270.2:c.1382A>G
- Protein (HGVS p.)
- NP_001263199.1:p.(Asn461Ser)
- GRCh38
- chr3:129433861 T>C
- GRCh37
- chr3:129152704 T>C
- ClinVar
- 1336001
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
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Transcript span
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Strand
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Variants mapped
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Source
UCSC ncbiRefSeqCurated
All variants in MBD4
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Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
3,262 / 1,614,054 alleles
AF 0.00202 · 8 homozygotes · FAF 0.00236
gnomAD v2.1
479 / 282,746 alleles
AF 0.00169 · 2 homozygotes · FAF 0.00254
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 0.002 · 3262 / 1,614,054 alleles · 8 hom · FAF 0.0024
| European (Finnish)203 / 64,008 | 0.00322 hom |
| European (non-Finnish)2872 / 1,179,952 | 0.00246 hom |
| Remaining individuals101 / 62,510 | 0.0016 |
| Ashkenazi Jewish28 / 29,602 | 0.00095 |
| African/African American30 / 75,036 | 0.0004 |
| South Asian19 / 91,078 | 0.00021 |
| Admixed American9 / 60,016 | 0.00015 |
0 alternate alleles recorded in 3 other groups: Amish, East Asian, Middle Eastern.
gnomAD v2.1
AF 0.0017 · 479 / 282,746 alleles · 2 hom · FAF 0.0025
| European (Finnish)78 / 25,108 | 0.0031 |
| European (non-Finnish)349 / 129,084 | 0.00272 hom |
| Remaining individuals18 / 7,216 | 0.0025 |
| Ashkenazi Jewish10 / 10,364 | 0.00096 |
| African/African American13 / 24,964 | 0.00052 |
| South Asian6 / 30,616 | 0.0002 |
| Admixed American5 / 35,440 | 0.00014 |
0 alternate alleles recorded in 1 other group: East Asian.
gnomAD-Canada
AF not recorded · ? / ? alleles
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0.002021; MAF= 0.20210%, 3262/1614054 alleles, homozygotes = 8) and has highest observed frequency in the European (Finnish) population (AF= 0.00317148; MAF= 0.31715%, 203/64008 alleles, homozygotes = 2); grpmax FAF= 0.00235897.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.0016941; MAF= 0.16941%, 479/282746 alleles, homozygotes = 2) and has highest observed frequency in the European (Finnish) population (AF= 0.00310658; MAF= 0.31066%, 78/25108 alleles, homozygotes = 0); grpmax FAF= 0.0025446.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.001628841350852427, 30/18418 alleles, homozygotes = 0).
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.540
- BayesDel
- -0.063
How the predictions were used
BP4 SupportingMultiple lines of computational evidence suggest no significant impact on the gene product. BayesDel scores -0.063 (benign) and SpliceAI predicts no splicing impact (max delta = 0.15). While REVEL scores 0.54 (borderline deleterious), the preponderance of in silico tools (2 of 3) supports a benign interpretation. Details ▾Hide ▴
Evidence considered
- BayesDel = -0.063 (benign)
- SpliceAI max delta = 0.15 (no splice impact). REVEL = 0.54 conflicts but does not override the two benign-supporting tools.
Sources
PP3 In silico predictors are conflicting. REVEL scores 0.54 (deleterious, >0.5 threshold), but BayesDel scores -0.063 (benign, <0 threshold) and SpliceAI predicts no splicing impact (max delta = 0.15). Only one of three computational tools supports a deleterious effect; multiple lines of concordant evidence are required for PP3. Details ▾Hide ▴
Evidence considered
- REVEL = 0.54 (deleterious)
- BayesDel = -0.063 (benign)
- SpliceAI max delta = 0.15 (no splice impact). Conflicting and insufficient for PP3.
Sources
BP7 N/AThis is a missense variant (c.1382A>G, p.Asn461Ser), not a synonymous (silent) variant. BP7 applies exclusively to synonymous variants with no predicted splice impact. Details ▾Hide ▴
Evidence considered
- Missense variant
- BP7 is specific to synonymous variants.
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.15). REVEL score = 0.54. BayesDel score = -0.0631527.
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
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PMID 25626707 ↗Whole-genome sequencing in newborn screening? A statement on the continued importance of targeted approaches in newborn screening programmes.Howard HC et al. · 2015Discusses the role of whole-genome sequencing in newborn screening programs. NM_001276270.2:c.1382A>G (p.Asn461Ser) was not identified in this paper.Does not name this variant
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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. NM_001276270.2:c.1382A>G (p.Asn461Ser) was not identified in the abstract.Does not name this variant
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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.Standards and guidelines for the interpretation of sequence variants (ACMG/AMP 2015). Provides the general classification framework but does not discuss MBD4 or NM_001276270.2:c.1382A>G (p.Asn461Ser).Does not name this variant
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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. · 2013Recommendations regarding newborn screening bloodspot collection device serial numbers on birth certificates. NM_001276270.2:c.1382A>G (p.Asn461Ser) was not identified.Does not name this variant
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PMID 23881473 ↗Newborn screening: education, consent, and the residual blood spot. The position of the national society of genetic counselors.Position statement on newborn screening education, consent, and residual blood spots. NM_001276270.2:c.1382A>G (p.Asn461Ser) was not identified.Does not name this variant
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PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Provides a refined classification framework but does not discuss MBD4 or NM_001276270.2:c.1382A>G.Does not name this variant
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PMID 31022120 ↗ACOG Committee Opinion No. 778 Summary: Newborn Screening and the Role of the Obstetrician-Gynecologist.ACOG Committee Opinion on newborn screening and the role of the obstetrician-gynecologist. NM_001276270.2:c.1382A>G (p.Asn461Ser) was not identified.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
3,262 / 1,614,054 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.150
Open source ↗
ClinVar
4 Likely benign · 2 Uncertain significance · 1 Likely Benign
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/1336001/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/3-129152704-T-C?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr3-129433861-T-C?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/3-129433861-T-C
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_001276270.2%3Ac.1…
- OncoKB ↗www.oncokb.org/gene/MBD4/N461S
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=MBD4+c.1382A%3EG
- 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= 0.002021; MAF= 0.20210%, 3262/1614054 alleles, homozygotes = 8) and has highest observed frequency in the European (Finnish) population (AF= 0.00317148; MAF= 0.31715%, 203/64008 alleles, homozygotes = 2); grpmax FAF= 0.00235897.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.0016941; MAF= 0.16941%, 479/282746 alleles, homozygotes = 2) and has highest observed frequency in the European (Finnish) population (AF= 0.00310658; MAF= 0.31066%, 78/25108 alleles, homozygotes = 0); grpmax FAF= 0.0025446.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.001628841350852427, 30/18418 alleles, homozygotes = 0).
ClinVar
This variant has been reported in ClinVar as Likely benign (4 clinical laboratories) and as Uncertain significance (2 clinical laboratories) and as Likely Benign (1 clinical laboratory). (ClinVarID = 1336001)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.15). REVEL score = 0.54. BayesDel score = -0.0631527.
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 not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.