About BARD1
No gene-level summary was recorded for this case.
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.
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.No gene-level summary was recorded for this case.
The recorded framework is Not recorded. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
The applied criteria and their strengths are shown as assessed under the stated framework.
No pathogenic criterion marked as applied in the recorded assessment.
gnomAD v4.1 reports an East Asian allele frequency of 2.11% (943/44,660 alleles) with 19 homozygotes, and a grpmax filtering allele frequency of 2.0%. These exceed the 1% BA1 threshold, establishing this variant as a common polymorphism incompatible with a highly penetrant Mendelian disease.
gnomAD v4.1 grpmax filtering allele frequency of 2.0% and East Asian allele frequency of 2.11% far exceed the 0.3% BS1 threshold. gnomAD v2.1 grpmax FAF of 0.12% is below 0.3% but superseded by the larger v4.1 dataset.
Multiple lines of computational evidence suggest no significant impact on the gene product. REVEL score is 0.312 (below pathogenic threshold), BayesDel score is -0.180 (benign range), and SpliceAI max delta score is 0.19 (no predicted splicing impact). Convergent benign predictions from independent in silico tools meet BP4 at supporting level.
ClinVar reports this variant as Benign by consensus of 9 clinical laboratories and Likely benign by 6 additional laboratories (ClinVar Variation ID 136497). The aggregate classification from multiple clinical testing laboratories is Benign, meeting BP6 at supporting level.
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, BP4 supporting, BP6 supporting; combination = 1 stand-alone benign + 1 strong benign + 2 supporting benign, which maps to Benign.
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1: 951 / 1,576,586 alleles. Recorded AF 0.000603202. Recorded homozygote count 19.
This variant is present in gnomAD v2.1 (AF= 0.000134099; MAF= 0.01341%, 29/216258 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.00168229; MAF= 0.16823%, 28/16644 alleles, homozygotes = 0); grpmax FAF= 0.00119534.
This variant is present in gnomAD-Canada v1.0 (AF= 0.00016286644951140066, 3/18420 alleles, homozygotes = 0).
Recorded SpliceAI maximum delta score: 0.190. Refer to the recorded PP3/BP4 rationale for interpretation.
9 Benign · 6 Likely benign.
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. BARD1, a tumor suppressor involved in the DNA damage response, is altered by mutation in breast and ovarian cancers.
This variant has not previously been reported in somatic cancers (COSMIC).
This variant does not lie in a statistically significant hotspot.
ACMG/AMP criteria under Not recorded, with the data and sources behind each one.
29 criteria with recorded statuses: 4 met · 19 not met · 0 not assessed · 6 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
This variant is present in gnomAD v4.1 at an East Asian allele frequency of 2.11% (943/44,660 alleles) with 19 homozygotes and a grpmax filtering allele frequency of 2.0%, exceeding the 1% BA1 stand-alone benign threshold and establishing it as a common polymorphism incompatible with a highly penetrant Mendelian disorder.
The variant is classified as Benign in ClinVar (Variation ID 136497) with consensus from 9 clinical testing laboratories reporting Benign and 6 reporting Likely benign.
Multiple in silico predictors are consistent with a benign effect: REVEL score 0.312, BayesDel score -0.180, and SpliceAI maximum delta score 0.19 indicate no significant impact on protein function or splicing.
The variant was listed among 11 BARD1 nsSNPs predicted as 'not tolerated' by SIFT (TI=0.04) in an in silico screening study (PMID:23056176), but was not classified as damaging by PolyPhen and was not among the four SNPs identified as deleterious by both methods. This in silico analysis does not alter the benign classification.
No variant-specific functional studies, de novo reports, or segregation data were identified. The variant has not been reported as pathogenic by any reputable source.
Final classification: Benign. BA1 (stand-alone benign) is met. BS1 (strong benign) and BP4, BP6 (supporting benign) provide additional support. No pathogenic criteria are met.
No criteria match.
No further detail was recorded.
No further detail was recorded.
No further detail was recorded.
Every interpreted variant in BARD1, mapped onto the exon structure of NM_000465.4. Select a row to find it on the plot.
| Protein | Location | Classification | Link |
|---|
| East Asian943 / 44,660 | 0.02119 hom |
| Remaining individuals8 / 60,750 | 0.00013 |
| East Asian28 / 16,644 | 0.0017 |
| Remaining individuals1 / 5,054 | 0.0002 |
This variant is present in gnomAD v4.1 (AF= 0.000603202; MAF= 0.06032%, 951/1576586 alleles, homozygotes = 19) and has highest observed frequency in the East Asian population (AF= 0.0211151; MAF= 2.11151%, 943/44660 alleles, homozygotes = 19); grpmax FAF= 0.0199964.
This variant is present in gnomAD v2.1 (AF= 0.000134099; MAF= 0.01341%, 29/216258 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.00168229; MAF= 0.16823%, 28/16644 alleles, homozygotes = 0); grpmax FAF= 0.00119534.
This variant is present in gnomAD-Canada v1.0 (AF= 0.00016286644951140066, 3/18420 alleles, homozygotes = 0).
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.19). REVEL score = 0.312. BayesDel score = -0.180224.
9 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata.
rs3738885 C/G S241C 0.04
Table 1 (SIFT Not Tolerated list); not present in Table 2 (PolyPhen Damaging list).
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
This variant is present in gnomAD v4.1 (AF= 0.000603202; MAF= 0.06032%, 951/1576586 alleles, homozygotes = 19) and has highest observed frequency in the East Asian population (AF= 0.0211151; MAF= 2.11151%, 943/44660 alleles, homozygotes = 19); grpmax FAF= 0.0199964.
This variant is present in gnomAD v2.1 (AF= 0.000134099; MAF= 0.01341%, 29/216258 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.00168229; MAF= 0.16823%, 28/16644 alleles, homozygotes = 0); grpmax FAF= 0.00119534.
This variant is present in gnomAD-Canada v1.0 (AF= 0.00016286644951140066, 3/18420 alleles, homozygotes = 0).
This variant has been reported in ClinVar as Benign (9 clinical laboratories) and as Likely benign (6 clinical laboratories). (ClinVarID = 136497)
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.19). REVEL score = 0.312. BayesDel score = -0.180224.
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. BARD1, a tumor suppressor involved in the DNA damage response, is altered by mutation in breast and ovarian cancers.
This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
This variant does not lie in a statistically significant hotspot.