rs7585356

Positions:

• chr2-214727582-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.86).
• 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/exons	MANE	Protein	UniProt
BARD1	NM_000465.4	c.*1094C>T		3_prime_UTR_variant	11/11	ENST00000260947.9	NP_000456.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BARD1	ENST00000260947.9	c.*1094C>T		3_prime_UTR_variant	11/11	1	NM_000465.4	ENSP00000260947	P2

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

Gnomad4 AFR exome AF: 0.165

Gnomad4 AMR exome AF: 0.247

Gnomad4 ASJ exome AF: 0.312

Gnomad4 EAS exome AF: 0.301

Gnomad4 SAS exome AF: 0.424

Gnomad4 FIN exome AF: 0.372

Gnomad4 NFE exome AF: 0.297

Gnomad4 OTH exome AF: 0.282

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

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.325

Gnomad4 EAS AF: 0.349

Gnomad4 SAS AF: 0.411

Gnomad4 FIN AF: 0.411

Gnomad4 NFE AF: 0.303

Gnomad4 OTH AF: 0.278

Alfa AF: 0.295 Hom.: 11433

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs7585356; hg19: chr2-215592306;