rs28997575

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 2P and 16B. PM4BP6_Very_StrongBA1

The NM_000465.4(BARD1):c.1075_1095delTTGCCTGAATGTTCTTCACCA(p.Leu359_Pro365del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.023 in 1,614,032 control chromosomes in the GnomAD database, including 759 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. L359L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.028 ( 85 hom., cov: 32)

Exomes 𝑓: 0.022 ( 674 hom. )

Consequence

BARD1
NM_000465.4 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:18

Conservation

PhyloP100: 2.10

Publications

19 publications found

Variant links:

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

BARD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

PM4

Nonframeshift variant in NON repetitive region in NM_000465.4.

BP6

Variant 2-214780778-GTGGTGAAGAACATTCAGGCAA-G is Benign according to our data. Variant chr2-214780778-GTGGTGAAGAACATTCAGGCAA-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 140795.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0711 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BARD1	NM_000465.4	MANE Select	c.1075_1095delTTGCCTGAATGTTCTTCACCA	p.Leu359_Pro365del	conservative_inframe_deletion	Exon 4 of 11	NP_000456.2	Q99728-1
BARD1	NM_001282543.2		c.1018_1038delTTGCCTGAATGTTCTTCACCA	p.Leu340_Pro346del	conservative_inframe_deletion	Exon 3 of 10	NP_001269472.1	Q99728-2
BARD1	NM_001282545.2		c.215+16262_215+16282delTTGCCTGAATGTTCTTCACCA		intron	N/A	NP_001269474.1	C9IYG1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BARD1	ENST00000260947.9	TSL:1 MANE Select	c.1075_1095delTTGCCTGAATGTTCTTCACCA	p.Leu359_Pro365del	conservative_inframe_deletion	Exon 4 of 11	ENSP00000260947.4	Q99728-1
BARD1	ENST00000617164.5	TSL:1	c.1018_1038delTTGCCTGAATGTTCTTCACCA	p.Leu340_Pro346del	conservative_inframe_deletion	Exon 3 of 10	ENSP00000480470.1	Q99728-2
BARD1	ENST00000613706.5	TSL:1	c.906+169_906+189delTTGCCTGAATGTTCTTCACCA		intron	N/A	ENSP00000484976.2	A0A087X2H0

Frequencies

GnomAD3 genomes

AF:

0.0282

AC:

4294

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0404

Gnomad AMI

AF:

0.0537

Gnomad AMR

AF:

0.0379

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.0478

Gnomad SAS

AF:

0.0774

Gnomad FIN

AF:

0.00179

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0183

Gnomad OTH

AF:

0.0316

GnomAD2 exomes

AF:

0.0289

AC:

7261

AN:

251308

AF XY:

0.0304

show subpopulations

Gnomad AFR exome

AF:

0.0432

Gnomad AMR exome

AF:

0.0337

Gnomad ASJ exome

AF:

0.0120

Gnomad EAS exome

AF:

0.0439

Gnomad FIN exome

AF:

0.00356

Gnomad NFE exome

AF:

0.0179

Gnomad OTH exome

AF:

0.0324

GnomAD4 exome

AF:

0.0224

AC:

32769

AN:

1461824

Hom.:

674

AF XY:

0.0238

AC XY:

17297

AN XY:

727208

show subpopulations

African (AFR)

AF:

0.0432

AC:

1447

AN:

33480

American (AMR)

AF:

0.0340

AC:

1521

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0120

AC:

313

AN:

26134

East Asian (EAS)

AF:

0.0583

AC:

2312

AN:

39690

South Asian (SAS)

AF:

0.0714

AC:

6162

AN:

86258

European-Finnish (FIN)

AF:

0.00311

AC:

166

AN:

53412

Middle Eastern (MID)

AF:

0.0349

AC:

201

AN:

5766

European-Non Finnish (NFE)

AF:

0.0171

AC:

19005

AN:

1111980

Other (OTH)

AF:

0.0272

AC:

1642

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.429

Heterozygous variant carriers

2178

4356

6533

8711

10889

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

802

1604

2406

3208

4010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0282

AC:

4294

AN:

152208

Hom.:

Cov.:

AF XY:

0.0284

AC XY:

2112

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.0405

AC:

1681

AN:

41522

American (AMR)

AF:

0.0379

AC:

579

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00778

AC:

AN:

3472

East Asian (EAS)

AF:

0.0477

AC:

247

AN:

5174

South Asian (SAS)

AF:

0.0776

AC:

374

AN:

4818

European-Finnish (FIN)

AF:

0.00179

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0183

AC:

1246

AN:

68004

Other (OTH)

AF:

0.0308

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

199

399

598

798

997

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00648

Hom.:

Bravo

AF:

0.0308

Asia WGS

AF:

0.0570

AC:

196

AN:

3478

EpiCase

AF:

0.0230

EpiControl

AF:

0.0226

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Familial cancer of breast (7)

Hereditary cancer-predisposing syndrome (4)

not specified (4)

not provided (2)

Hereditary breast ovarian cancer syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.1

Mutation Taster

=172/28

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over