2-214757506-A-T

Variant names:

• chr2-214757506-A-T
• rs10190829
• NM_000465.4:c.1569-4951T>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000465.4(BARD1):​c.1569-4951T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 151,868 control chromosomes in the GnomAD database, including 15,038 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.44 (15038 hom., cov: 31)
• Consequence: BARD1 NM_000465.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BARD1	NM_000465.4	c.1569-4951T>A		intron_variant	Intron 6 of 10	ENST00000260947.9	NP_000456.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BARD1	ENST00000260947.9	c.1569-4951T>A		intron_variant	Intron 6 of 10	1	NM_000465.4	ENSP00000260947.4

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67366 AN: 151748 Hom.: 15016 Cov.: 31

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.415

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.489

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.458

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.444 AC: 67416 AN: 151868 Hom.: 15038 Cov.: 31 AF XY: 0.449 AC XY: 33305 AN XY: 74216

Gnomad4 AFR AF: 0.480

Gnomad4 AMR AF: 0.395

Gnomad4 ASJ AF: 0.436

Gnomad4 EAS AF: 0.419

Gnomad4 SAS AF: 0.502

Gnomad4 FIN AF: 0.489

Gnomad4 NFE AF: 0.424

Gnomad4 OTH AF: 0.457

Alfa AF: 0.300 Hom.: 740

Bravo AF: 0.431

Asia WGS AF: 0.455 AC: 1578 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.74
DANN	Benign	0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10190829; hg19: chr2-215622230;