rs3768708

Variant names:

• chr2-214780322-C-T
• rs3768708
• NM_000465.4:c.1314+238G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-214780322-C-T
• chr2-214780322-C-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000465.4(BARD1):​c.1314+238G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 152,062 control chromosomes in the GnomAD database, including 39,357 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.71 (39357 hom., cov: 32)
• Consequence: BARD1 NM_000465.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0480
• Publications: 11 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):

• BARD1-related cancer predisposition

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• breast cancer

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

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

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 2-214780322-C-T is Benign according to our data. Variant chr2-214780322-C-T is described in ClinVar as Benign. ClinVar VariationId is 1280386.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000465.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BARD1	NM_000465.4	MANE Select	c.1314+238G>A		intron	N/A	NP_000456.2	Q99728-1
	BARD1	NM_001282543.2		c.1257+238G>A		intron	N/A	NP_001269472.1	Q99728-2
	BARD1	NM_001282545.2		c.215+16739G>A		intron	N/A	NP_001269474.1	C9IYG1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BARD1	ENST00000260947.9	TSL:1 MANE Select	c.1314+238G>A		intron	N/A	ENSP00000260947.4	Q99728-1
	BARD1	ENST00000617164.5	TSL:1	c.1257+238G>A		intron	N/A	ENSP00000480470.1	Q99728-2
	BARD1	ENST00000613706.5	TSL:1	c.906+646G>A		intron	N/A	ENSP00000484976.2	A0A087X2H0

Frequencies

GnomAD3 genomes AF: 0.715 AC: 108577 AN: 151944 Hom.: 39336 Cov.: 32

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.758

Gnomad AMR AF: 0.718

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.793

Gnomad SAS AF: 0.687

Gnomad FIN AF: 0.857

Gnomad MID AF: 0.755

Gnomad NFE AF: 0.761

Gnomad OTH AF: 0.717

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

GnomAD4 genome AF: 0.714 AC: 108645 AN: 152062 Hom.: 39357 Cov.: 32 AF XY: 0.720 AC XY: 53509 AN XY: 74322

African (AFR) AF: 0.589 AC: 24401 AN: 41434

American (AMR) AF: 0.718 AC: 10961 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.752 AC: 2607 AN: 3468

East Asian (EAS) AF: 0.792 AC: 4094 AN: 5166

South Asian (SAS) AF: 0.688 AC: 3319 AN: 4822

European-Finnish (FIN) AF: 0.857 AC: 9099 AN: 10612

Middle Eastern (MID) AF: 0.764 AC: 223 AN: 292

European-Non Finnish (NFE) AF: 0.761 AC: 51730 AN: 67982

Other (OTH) AF: 0.720 AC: 1520 AN: 2110

Alfa AF: 0.743 Hom.: 159732

Bravo AF: 0.697

Asia WGS AF: 0.733 AC: 2546 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.4
DANN	Benign	0.71
PhyloP100		-0.048
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: rs3768708; hg19: chr2-215645046;