rs16852600

Variant names:

• chr2-214730921-C-T
• rs16852600
• ENST00000471590.5:n.225G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000471590.5(BARD1):​n.225G>A variant causes a non coding transcript exon 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 ENST00000471590.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.88
• Publications: 21 publications found

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]

BARD1 Gene-Disease associations (from GenCC):

• breast cancer

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• hereditary breast carcinoma

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
• familial ovarian cancer

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• hereditary nonpolyposis colon cancer

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.059).
• 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 rank	MANE	Protein	UniProt
BARD1	NM_000465.4	c.1904-413G>A		intron_variant	Intron 9 of 10	ENST00000260947.9	NP_000456.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BARD1	ENST00000260947.9	c.1904-413G>A		intron_variant	Intron 9 of 10	1	NM_000465.4	ENSP00000260947.4

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

GnomAD2 exomes AF: 0.305 AC: 41630 AN: 136526 AF XY: 0.315

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 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

African (AFR) AF: 0.158 AC: 1366 AN: 8632

American (AMR) AF: 0.249 AC: 6747 AN: 27066

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 3354 AN: 10714

East Asian (EAS) AF: 0.329 AC: 3024 AN: 9190

South Asian (SAS) AF: 0.399 AC: 23528 AN: 59010

European-Finnish (FIN) AF: 0.405 AC: 5132 AN: 12672

Middle Eastern (MID) AF: 0.291 AC: 805 AN: 2770

European-Non Finnish (NFE) AF: 0.298 AC: 47175 AN: 158154

Other (OTH) AF: 0.300 AC: 4250 AN: 14178

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

African (AFR) AF: 0.163 AC: 6753 AN: 41486

American (AMR) AF: 0.256 AC: 3912 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1120 AN: 3468

East Asian (EAS) AF: 0.345 AC: 1778 AN: 5150

South Asian (SAS) AF: 0.410 AC: 1980 AN: 4826

European-Finnish (FIN) AF: 0.410 AC: 4326 AN: 10546

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.293 AC: 19919 AN: 67978

Other (OTH) AF: 0.263 AC: 554 AN: 2110

Alfa AF: 0.292 Hom.: 4231

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
PhyloP100		2.9
PromoterAI		-0.015	Neutral
Mutation Taster		=160/40	polymorphism (auto)

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

Other links and lift over

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