rs7585356

Variant names:

• chr2-214727582-G-A
• rs7585356
• NM_000465.4:c.*1094C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000465.4(BARD1):​c.*1094C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 232,140 control chromosomes in the GnomAD database, including 9,763 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 0.28 (6310 hom., cov: 32)
  • Exomes 𝑓: 0.29 (3453 hom.)
• Consequence: BARD1 NM_000465.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.848
• Publications: 16 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BARD1	NM_000465.4	c.*1094C>T		3_prime_UTR_variant	Exon 11 of 11	ENST00000260947.9	NP_000456.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BARD1	ENST00000260947.9	c.*1094C>T		3_prime_UTR_variant	Exon 11 of 11	1	NM_000465.4	ENSP00000260947.4

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41952 AN: 151978 Hom.: 6302 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.287

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.274

GnomAD4 exome AF: 0.291 AC: 23281 AN: 80044 Hom.: 3453 Cov.: 0 AF XY: 0.294 AC XY: 10851 AN XY: 36854

African (AFR) AF: 0.165 AC: 629 AN: 3822

American (AMR) AF: 0.247 AC: 610 AN: 2470

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 1572 AN: 5036

East Asian (EAS) AF: 0.301 AC: 3400 AN: 11282

South Asian (SAS) AF: 0.424 AC: 301 AN: 710

European-Finnish (FIN) AF: 0.372 AC: 64 AN: 172

Middle Eastern (MID) AF: 0.305 AC: 146 AN: 478

European-Non Finnish (NFE) AF: 0.297 AC: 14679 AN: 49400

Other (OTH) AF: 0.282 AC: 1880 AN: 6674

GnomAD4 genome AF: 0.276 AC: 41968 AN: 152096 Hom.: 6310 Cov.: 32 AF XY: 0.283 AC XY: 21054 AN XY: 74322

African (AFR) AF: 0.172 AC: 7140 AN: 41502

American (AMR) AF: 0.267 AC: 4076 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 1128 AN: 3468

East Asian (EAS) AF: 0.349 AC: 1802 AN: 5168

South Asian (SAS) AF: 0.411 AC: 1981 AN: 4818

European-Finnish (FIN) AF: 0.411 AC: 4339 AN: 10562

Middle Eastern (MID) AF: 0.291 AC: 85 AN: 292

European-Non Finnish (NFE) AF: 0.303 AC: 20603 AN: 67980

Other (OTH) AF: 0.278 AC: 587 AN: 2112

Alfa AF: 0.291 Hom.: 25073

Bravo AF: 0.254

Asia WGS AF: 0.352 AC: 1226 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.47
DANN	Benign	0.44
PhyloP100		-0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	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: rs7585356; hg19: chr2-215592306;