rs16852600

chr2-214730921-C-T

Variant summary

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

The NM_000465.4(BARD1):c.1904-413G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 454,442 control chromosomes in the GnomAD database, including 21,896 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 0.27 (5983 hom., cov: 32)
  • Exomes 𝑓: 0.32 (15913 hom.)
• Consequence: BARD1 NM_000465.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.88

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=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BARD1	NM_000465.4	c.1904-413G>A		intron_variant		ENST00000260947.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BARD1	ENST00000260947.9	c.1904-413G>A		intron_variant		1	NM_000465.4	P2

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40640 AN: 151938 Hom.: 5977 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.345

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.260

GnomAD3 exomes AF: 0.305 AC: 41630 AN: 136526 Hom.: 6687 AF XY: 0.315 AC XY: 23333 AN XY: 74000

Gnomad AFR exome AF: 0.159

Gnomad AMR exome AF: 0.249

Gnomad ASJ exome AF: 0.315

Gnomad EAS exome AF: 0.341

Gnomad SAS exome AF: 0.396

Gnomad FIN exome AF: 0.408

Gnomad NFE exome AF: 0.290

Gnomad OTH exome AF: 0.283

GnomAD4 exome AF: 0.315 AC: 95381 AN: 302386 Hom.: 15913 Cov.: 0 AF XY: 0.326 AC XY: 56146 AN XY: 172140

Gnomad4 AFR exome AF: 0.158

Gnomad4 AMR exome AF: 0.249

Gnomad4 ASJ exome AF: 0.313

Gnomad4 EAS exome AF: 0.329

Gnomad4 SAS exome AF: 0.399

Gnomad4 FIN exome AF: 0.405

Gnomad4 NFE exome AF: 0.298

Gnomad4 OTH exome AF: 0.300

GnomAD4 genome AF: 0.267 AC: 40654 AN: 152056 Hom.: 5983 Cov.: 32 AF XY: 0.276 AC XY: 20506 AN XY: 74320

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.345

Gnomad4 SAS AF: 0.410

Gnomad4 FIN AF: 0.410

Gnomad4 NFE AF: 0.293

Gnomad4 OTH AF: 0.263

Alfa AF: 0.292 Hom.: 3878

Bravo AF: 0.244

Asia WGS AF: 0.344 AC: 1197 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	7.9
Dann	Benign	0.77

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: rs16852600; hg19: chr2-215595645; COSMIC: COSV53612285; COSMIC: COSV53612285;