rs199846428
Positions:
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate
The NM_000465.4(BARD1):c.216-12A>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00013 ( 0 hom., cov: 29)
Exomes 𝑓: 0.000039 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
BARD1
NM_000465.4 splice_polypyrimidine_tract, intron
NM_000465.4 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.00004557
2
Clinical Significance
Conservation
PhyloP100: -0.528
Genes affected
BARD1 (HGNC:952): (BRCA1 associated RING domain 1) This gene encodes a protein which interacts with the N-terminal region of BRCA1. In addition to its ability to bind BRCA1 in vivo and in vitro, it shares homology with the 2 most conserved regions of BRCA1: the N-terminal RING motif and the C-terminal BRCT domain. The RING motif is a cysteine-rich sequence found in a variety of proteins that regulate cell growth, including the products of tumor suppressor genes and dominant protooncogenes. This protein also contains 3 tandem ankyrin repeats. The BARD1/BRCA1 interaction is disrupted by tumorigenic amino acid substitutions in BRCA1, implying that the formation of a stable complex between these proteins may be an essential aspect of BRCA1 tumor suppression. This protein may be the target of oncogenic mutations in breast or ovarian cancer. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
Variant 2-214792457-T-A is Benign according to our data. Variant chr2-214792457-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 801889.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BARD1 | NM_000465.4 | c.216-12A>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000260947.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BARD1 | ENST00000260947.9 | c.216-12A>T | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000465.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 15AN: 114574Hom.: 0 Cov.: 29 FAILED QC
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GnomAD3 exomes AF: 0.0000869 AC: 8AN: 92048Hom.: 0 AF XY: 0.000119 AC XY: 6AN XY: 50276
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000388 AC: 52AN: 1338870Hom.: 0 Cov.: 33 AF XY: 0.0000317 AC XY: 21AN XY: 662054
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GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.000131 AC: 15AN: 114574Hom.: 0 Cov.: 29 AF XY: 0.0000905 AC XY: 5AN XY: 55256
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Familial cancer of breast Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at