About MBD4
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
MBD4 c.682G>C, p.(Val228Leu)
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: 1
Benign evidence criteria: 1
Pathogenic criteria applied · 1
PM2Supporting
PM2 · supporting
NM_003925.3:c.682G>C is present at extremely low frequency in population databases: gnomAD v2.1 overall allele frequency is 0.011% (31/282,140 alleles) and gnomAD v4.1 overall allele frequency is 0.0079% (127/1,614,038 alleles), both below the 0.1% PM2 threshold. No homozygotes are observed. The highest subpopulation frequency is in the Finnish population at 0.032% (v2.1), also well below 0.1%.
Benign criteria applied · 1
BP4Supporting
BP4 · supporting
Multiple lines of computational evidence unanimously predict a benign effect: REVEL score 0.199, BayesDel score −0.381, SpliceAI max delta 0.00, and CADD 7.985. Repo et al. 2020 also reported in silico predictions as polymorphism (MutationTaster), benign (PolyPhen), tolerated (SIFT), and no splicing impact (HSF), supporting BP4 at supporting strength.
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: PM2 supporting, BP4 supporting; combination = 1 supporting + 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
127 / 1,614,038 alleles
gnomAD v4.1: 127 / 1,614,038 alleles. Recorded AF 7.86846e-05. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000109875; MAF= 0.01099%, 31/282140 alleles, homozygotes = 0) and has highest observed frequency in the European (Finnish) population (AF= 0.000318522; MAF= 0.03185%, 8/25116 alleles, homozygotes = 0); grpmax FAF= 0.00030441.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
SpliceAI score
0.000 maximum delta
Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
2 reported laboratory submissions
1 Likely benign · 1 Uncertain significance. 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.
29 criteria with recorded statuses: 2 met · 20 not met · 0 not assessed · 7 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_003925.3:c.682G>C (p.Val228Leu) is a missense variant in MBD4 exon 3, observed at extremely low frequency in population databases (gnomAD v2.1 AF = 0.011%, 31/282,140 alleles; gnomAD v4.1 AF = 0.0079%, 127/1,614,038 alleles; no homozygotes).
Multiple in silico tools unanimously predict a benign effect: REVEL score 0.199, BayesDel score −0.381, SpliceAI max delta 0.00, and CADD 7.985. Repo et al. (2020) also reported in silico predictions as polymorphism, benign, tolerated, and no splicing impact.
This variant has been reported in ClinVar as Likely benign by Ambry Genetics (SCV005618014) and as Uncertain significance by Invitae (SCV003476936). No expert panel review has been performed (ClinVar Variation ID: 2163156).
The variant was identified in 1 of 440 Finnish patients with uveal melanoma (Repo et al. 2020). The authors considered it likely benign based on in silico predictions and noted no enrichment in cases compared to the Finnish population frequency (0.032%).
No functional studies, segregation data, de novo observations, or case-control association data are available for this variant. MBD4 is not an established gene where missense variants are a common disease mechanism; the primary pathogenic mechanism is loss of function via truncating variants.
Based on generic ACMG/AMP 2015 criteria, the evidence profile consists of PM2_supporting (low population frequency) and BP4_supporting (multiple benign in silico predictions). These opposing criteria result in an overall classification of Uncertain significance.
No criteria match.
Met · 2
PM2 SupportingNM_003925.3:c.682G>C is present at extremely low frequency in population databases: gnomAD v2.1 overall allele frequency is 0.011% (31/282,140 alleles) and gnomAD v4.1 overall allele frequency is 0.0079% (127/1,614,038 alleles), both below the 0.1% PM2 threshold. No homozygotes are observed. The highest subpopulation frequency is in the Finnish population at 0.032% (v2.1), also well below 0.1%. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: AF = 0.011%
- 31/282
- 140 alleles
- 0 homozygotes.
- gnomAD v4.1: AF = 0.0079%
- 127/1
- 614
- 038 alleles
- grpmax FAF v4.1 = 7.57e-05.
Sources
BP4 SupportingMultiple lines of computational evidence unanimously predict a benign effect: REVEL score 0.199, BayesDel score −0.381, SpliceAI max delta 0.00, and CADD 7.985. Repo et al. 2020 also reported in silico predictions as polymorphism (MutationTaster), benign (PolyPhen), tolerated (SIFT), and no splicing impact (HSF), supporting BP4 at supporting strength. Details ▾Hide ▴
Evidence considered
- REVEL: 0.199 (benign).
- BayesDel: −0.381 (benign).
- SpliceAI: max delta 0.00 (no splice impact).
- CADD: 7.985.
- Repo et al. 2020 Table 1: polymorphism
- benign
- tolerated
- no splicing impact.
Sources
Not met · 20 · evaluated, threshold not reached
PS2 No de novo observation of NM_003925.3:c.682G>C has been reported in any reviewed publication or database. Details ▾Hide ▴
Evidence considered
- No de novo report found in ClinVar or full-text literature.
Sources
PS3 No variant-specific functional assay for NM_003925.3:c.682G>C (p.Val228Leu) was identified. The one paper that examined this variant (Repo et al. 2020, PMID:32421892) relied solely on in silico predictions and did not perform any functional characterization. Details ▾Hide ▴
Evidence considered
- Repo et al. 2020 considered the variant likely benign based on in silico predictions only.
- OncoKB reports Unknown Oncogenic Effect with no variant-specific reviewed functional evidence.
Still missing
- No functional assay data available for V228L.
Sources
PS4 The variant was observed in 1 of 440 Finnish uveal melanoma patients (Repo et al. 2020), yielding a prevalence of 0.23% in cases, which is comparable to the Finnish population allele frequency of 0.032% (gnomAD v2.1). No case-control enrichment or statistical evidence supporting pathogenicity exists. Details ▾Hide ▴
Evidence considered
- Observed in 1/440 UM cases vs. 8/25
- 116 Finnish population alleles (Repo et al. 2020).
- No statistically significant enrichment in affected individuals.
Sources
PM1 The variant resides in exon 3 of MBD4, within the methyl-CpG binding domain region, but residue Val228 is not located in a statistically significant mutational hotspot, and no functional domain-specific constraint evidence supports PM1. Details ▾Hide ▴
Evidence considered
- Hotspot analysis: residue not statistically significant.
- No established critical domain with enrichment of pathogenic missense variants at this residue.
PM6 No de novo observation of NM_003925.3:c.682G>C has been reported; no maternity/paternity confirmation data exist for this variant. Details ▾Hide ▴
PP1 No family segregation data are available for NM_003925.3:c.682G>C in any reviewed publication or database. Details ▾Hide ▴
Evidence considered
- No segregation analysis reported.
Still missing
- No family studies available.
PP2 MBD4 is not a gene in which missense variants are a recognized common mechanism of disease. The established disease mechanism for MBD4 is loss of function (truncating variants). The gene has a low pLI of 0 and is tolerant to missense variation. Details ▾Hide ▴
Evidence considered
- MBD4 disease mechanism is loss of function via truncating variants.
- gnomAD constraint: pLI = 0
- missense o/e = 0.88 (tolerant).
Sources
pvs1_gene_contextPMID:32421892 ↗
PP3 Multiple in silico tools unanimously predict a benign effect: REVEL score 0.199 (below the 0.29 benign threshold), BayesDel score −0.381 (negative scores favor benign), SpliceAI max delta 0.00 (no splicing impact), and CADD 7.985 (below common pathogenicity thresholds). These results do not support PP3. Details ▾Hide ▴
Evidence considered
- REVEL: 0.199 (benign).
- BayesDel: −0.381 (benign).
- SpliceAI: max delta 0.00.
- CADD: 7.985.
- Repo et al. 2020 Table 1: polymorphism
- benign
- tolerated
- no splicing impact.
Sources
PP4 No specific patient phenotype data for NM_003925.3:c.682G>C carriers are available that would allow evaluation of phenotype specificity. The single carrier in Repo et al. 2020 was a Finnish uveal melanoma patient, but the variant was considered likely benign by the authors. Details ▾Hide ▴
Evidence considered
- One carrier reported with uveal melanoma
- but no detailed phenotype specificity data.
Still missing
- No detailed phenotype information for carriers.
Sources
PP5 No reputable source has independently classified NM_003925.3:c.682G>C as pathogenic. The ClinVar submissions are Likely benign (Ambry Genetics) and Uncertain significance (Invitae). PP5 requires a pathogenic classification from a reputable source, which is not met here. Details ▾Hide ▴
Evidence considered
- ClinVar: Likely benign (1 submitter
- criteria provided)
- Uncertain significance (1 submitter
- criteria provided).
- No expert panel or reputable source classification as pathogenic.
Sources
BA1 The overall allele frequency in gnomAD v2.1 is 0.011%, well below the BA1 threshold of >1%. The variant is rare, not common, in population databases. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 AF = 0.011% (below 1% BA1 threshold).
- gnomAD v4.1 AF = 0.0079%.
Sources
BS1 The overall allele frequency in gnomAD v2.1 is 0.011%, well below the BS1 threshold of >0.3%. The highest subpopulation frequency is Finnish at 0.032%, also below the threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 AF = 0.011%
- Finnish subpop AF = 0.032% (below 0.3% BS1 threshold).
- gnomAD v4.1 AF = 0.0079%.
Sources
BS2 No evidence of observation in healthy adult controls specifically documented for this variant. While the variant is present in gnomAD (presumed healthy population), the total allele count is low (31 in v2.1, 127 in v4.1), and no dedicated control cohort study has confirmed benign observation in a sufficient number of healthy individuals. Details ▾Hide ▴
Evidence considered
- Variant present at very low frequency in population databases
- insufficient to meet BS2.
Sources
BS3 No functional studies demonstrating a benign effect of NM_003925.3:c.682G>C (p.Val228Leu) have been performed. The assessment of likely benign in Repo et al. 2020 was based solely on in silico predictions, not functional assays. Details ▾Hide ▴
Evidence considered
- Repo et al. 2020: no functional assay
- benign assessment based on in silico predictions only.
Still missing
- No functional assay data for V228L.
Sources
BS4 No segregation data are available for NM_003925.3:c.682G>C. BS4 requires lack of cosegregation with disease in affected family members, which cannot be assessed. Details ▾Hide ▴
Evidence considered
- No family segregation data available.
Still missing
- No segregation studies.
BP1 Although MBD4 disease mechanism is primarily loss of function via truncating variants, the missense variant NM_003925.3:c.682G>C cannot automatically be considered benign under BP1. The gene is not established with a clear rule that missense variants are exclusively benign; some MBD4 missense variants (e.g., Asp568His) have shown functional impact. Details ▾Hide ▴
Evidence considered
- MBD4 has LOF disease mechanism
- but some missense variants (e.g.
- D568H) show deleterious effects.
- BP1 requires the gene to have only truncating variants as disease-causing
- which is not established for MBD4.
Sources
pvs1_gene_contextPMID:32421892 ↗
BP2 No observation of NM_003925.3:c.682G>C in trans with a known pathogenic MBD4 variant has been reported. Without such data, BP2 cannot be applied. Details ▾Hide ▴
Evidence considered
- No observation in trans with pathogenic variant.
BP5 No alternate molecular basis for disease has been identified in individuals carrying NM_003925.3:c.682G>C. BP5 requires observation of the variant in a case with an alternate confirmed genetic cause, which has not been reported. Details ▾Hide ▴
Evidence considered
- No alternate molecular cause identified in variant carriers.
BP6 No reputable source has independently classified NM_003925.3:c.682G>C as benign. While Ambry Genetics submitted a Likely benign classification, this is a single submitter without expert panel review. BP6 requires a reputable source classification as benign, which is not met here. Details ▾Hide ▴
Evidence considered
- ClinVar: Likely benign (1 submitter)
- but no expert panel or multi-submitter consensus benign classification.
Sources
PS5 No reputable source has classified NM_003925.3:c.682G>C as pathogenic. ClinVar submissions are Likely benign (Ambry Genetics) and Uncertain significance (Invitae), neither meeting the pathogenic threshold required for PS5. Details ▾Hide ▴
Evidence considered
- ClinVar classification is Likely benign (1 submitter) and Uncertain significance (1 submitter)
- no pathogenic classification.
Sources
Not applicable · 7· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_003925.3:c.682G>C is a missense variant (p.Val228Leu) and does not fall into the null-variant categories of nonsense, frameshift, or canonical ±1,2 splice consensus variants required for PVS1 application. Details ▾Hide ▴
Evidence considered
- Variant is a missense substitution
- not a null variant.
- Generic PVS1 framework (PMC6185798) does not apply to missense variants.
Sources
pvs1_variant_assessmentpvs1_generic_framework ↗
PS1 N/ANo previously classified pathogenic variant at the same amino acid residue (Val228) was identified. PM5 candidate harvesting found no same-residue comparator variants with established pathogenicity. Details ▾Hide ▴
Evidence considered
- No pathogenic variant at Val228 in ClinVar or literature.
Sources
pm5_candidates
PM3 N/APM3 applies to recessive disorders. MBD4-associated conditions are not established as autosomal recessive; the disease mechanism is autosomal dominant with loss of function. Details ▾Hide ▴
Sources
pvs1_gene_context
PM4 N/ANM_003925.3:c.682G>C is a missense substitution and does not alter protein length. PM4 applies to non-frameshift and stop-loss variants that change protein length. Details ▾Hide ▴
No further detail was recorded.
PM5 N/AUnable to confirm classic same-residue PM5 semantics safely; no same-residue comparator variants with established pathogenicity were identified at Val228. Details ▾Hide ▴
Evidence considered
- PM5 candidate harvesting found no same-residue candidates with established pathogenicity.
Sources
pm5_candidates
BP3 N/ANM_003925.3:c.682G>C is a substitution, not an in-frame deletion/insertion. BP3 applies only to in-frame indels in repetitive regions. Details ▾Hide ▴
No further detail was recorded.
BP7 N/ANM_003925.3:c.682G>C is a missense variant (p.Val228Leu), not a synonymous variant. BP7 applies only to synonymous variants without predicted splice impact. Details ▾Hide ▴
Evidence considered
- Variant is missense
- not synonymous.
Identifiers
- Gene
- MBD4
- Transcript
- NM_003925.3
- Coding (HGVS c.)
- NM_003925.3:c.682G>C
- Protein (HGVS p.)
- NP_003916.1:p.(Val228Leu)
- GRCh38
- chr3:129436962 C>G
- GRCh37
- chr3:129155805 C>G
- ClinVar
- 2163156
Gene diagram
Every interpreted variant in MBD4, mapped onto the exon structure of NM_003925.3. Select a row to find it on the plot.
MBD4NM_003925.3
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
127 / 1,614,038 alleles
AF 7.87e-05 · 0 homozygotes · FAF 7.57e-05
gnomAD v2.1
31 / 282,140 alleles
AF 0.00011 · 0 homozygotes · FAF 0.000304
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 7.9e-05 · 127 / 1,614,038 alleles · 0 hom · FAF 7.6e-05
| European (Finnish)19 / 63,998 | 0.0003 |
| European (non-Finnish)106 / 1,180,050 | 9e-05 |
| Remaining individuals2 / 62,488 | 3.2e-05 |
0 alternate alleles recorded in 7 other groups: Admixed American, Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American.
gnomAD v2.1
AF 0.00011 · 31 / 282,140 alleles · 0 hom · FAF 0.0003
| European (Finnish)8 / 25,116 | 0.00032 |
| European (non-Finnish)23 / 128,546 | 0.00018 |
0 alternate alleles recorded in 6 other groups: African/African American, Admixed American, Ashkenazi Jewish, East Asian, Remaining individuals, South Asian.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 7.86846e-05; MAF= 0.00787%, 127/1614038 alleles, homozygotes = 0) and has highest observed frequency in the European (Finnish) population (AF= 0.000296884; MAF= 0.02969%, 19/63998 alleles, homozygotes = 0); grpmax FAF= 7.573e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000109875; MAF= 0.01099%, 31/282140 alleles, homozygotes = 0) and has highest observed frequency in the European (Finnish) population (AF= 0.000318522; MAF= 0.03185%, 8/25116 alleles, homozygotes = 0); grpmax FAF= 0.00030441.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.199
- BayesDel
- -0.381
How the predictions were used
BP4 SupportingMultiple lines of computational evidence unanimously predict a benign effect: REVEL score 0.199, BayesDel score −0.381, SpliceAI max delta 0.00, and CADD 7.985. Repo et al. 2020 also reported in silico predictions as polymorphism (MutationTaster), benign (PolyPhen), tolerated (SIFT), and no splicing impact (HSF), supporting BP4 at supporting strength. Details ▾Hide ▴
Evidence considered
- REVEL: 0.199 (benign).
- BayesDel: −0.381 (benign).
- SpliceAI: max delta 0.00 (no splice impact).
- CADD: 7.985.
- Repo et al. 2020 Table 1: polymorphism
- benign
- tolerated
- no splicing impact.
Sources
PP3 Multiple in silico tools unanimously predict a benign effect: REVEL score 0.199 (below the 0.29 benign threshold), BayesDel score −0.381 (negative scores favor benign), SpliceAI max delta 0.00 (no splicing impact), and CADD 7.985 (below common pathogenicity thresholds). These results do not support PP3. Details ▾Hide ▴
Evidence considered
- REVEL: 0.199 (benign).
- BayesDel: −0.381 (benign).
- SpliceAI: max delta 0.00.
- CADD: 7.985.
- Repo et al. 2020 Table 1: polymorphism
- benign
- tolerated
- no splicing impact.
Sources
BP7 N/ANM_003925.3:c.682G>C is a missense variant (p.Val228Leu), not a synonymous variant. BP7 applies only to synonymous variants without predicted splice impact. Details ▾Hide ▴
Evidence considered
- Variant is missense
- not synonymous.
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.199. BayesDel score = -0.380622.
6 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata.
Recorded publications
-
PMID 23619275 ↗ACMG position statement on prenatal/preconception expanded carrier screening.ACMG policy statement on prenatal/preconception expanded carrier screening criteria. NM_003925.3:c.682G>C was not mentioned or relevant to this paper.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.Edwards JG et al. · 2015Joint statement on expanded carrier screening in reproductive medicine from ACMG, ACOG, NSGC, and others. NM_003925.3:c.682G>C was not mentioned or relevant to this paper.Does not name this variant
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PMID 32421892 ↗Germline loss-of-function variants in MBD4 are rare in Finnish patients with uveal melanoma.Repo P et al. · 2020NM_003925.3:c.682G>C (p.Val228Leu) was identified in 1 of 440 Finnish patients with uveal melanoma. In silico predictions classified the variant as polymorphism (MutationTaster), benign (PolyPhen), tolerated (SIFT), with no predicted splicing impact (HSF) and CADD 7.985. The authors considered this and other exon 3 missense variants likely benign based on in silico evidence without further functional characterization.Names this variant
Quoted passage
Three rare exon 3 missense variants, c.682G>C (rs140696334, Val228Leu), c.1036G>A (rs140693, Glu346Lys) and c.1073T>C (rs2307298, Ile358Thr) were identified in 6 patients... Based on in silico predictions (Table 1) and without further evidence, we consider the exon 3 variants to be likely benign.
Results, paragraph 4; Table 1
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PMID 24121147 ↗Appropriateness of newborn screening for α1-antitrypsin deficiency.Teckman J et al. · 2014Discusses the appropriateness of newborn screening for alpha-1-antitrypsin deficiency. NM_003925.3:c.682G>C was not mentioned or relevant to this paper.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_003925.3:c.682G>C was not mentioned in this paper.Does not name this variant
-
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_003925.3:c.682G>C was not mentioned in this paper.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
127 / 1,614,038 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.000
Open source ↗
ClinVar
1 Likely benign · 1 Uncertain significance
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/2163156/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/3-129155805-C-G?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr3-129436962-C-G?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/3-129436962-C-G
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_003925.3%3Ac.682G…
- OncoKB ↗www.oncokb.org/gene/MBD4/V228L
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=MBD4+c.682G%3EC
- 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= 7.86846e-05; MAF= 0.00787%, 127/1614038 alleles, homozygotes = 0) and has highest observed frequency in the European (Finnish) population (AF= 0.000296884; MAF= 0.02969%, 19/63998 alleles, homozygotes = 0); grpmax FAF= 7.573e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000109875; MAF= 0.01099%, 31/282140 alleles, homozygotes = 0) and has highest observed frequency in the European (Finnish) population (AF= 0.000318522; MAF= 0.03185%, 8/25116 alleles, homozygotes = 0); grpmax FAF= 0.00030441.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Likely benign (1 clinical laboratory) and as Uncertain significance (1 clinical laboratory). (ClinVarID = 2163156)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.199. BayesDel score = -0.380622.
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.