NM_000465.4:c.*119G>A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_000465.4(BARD1):c.*119G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00045 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

BARD1
NM_000465.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.866

Publications

0 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
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: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 2-214728557-C-T is Benign according to our data. Variant chr2-214728557-C-T is described in ClinVar as Benign. ClinVar VariationId is 801877.Status of the report is criteria_provided_single_submitter, 1 stars.

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	Effect	Exon Rank	Protein	UniProt
BARD1	NM_000465.4	MANE Select	c.*119G>A	3_prime_UTR	Exon 11 of 11	NP_000456.2	Q99728-1
BARD1	NM_001282543.2		c.*119G>A	3_prime_UTR	Exon 10 of 10	NP_001269472.1	Q99728-2
BARD1	NM_001282545.2		c.*119G>A	3_prime_UTR	Exon 7 of 7	NP_001269474.1	C9IYG1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BARD1	ENST00000260947.9	TSL:1 MANE Select	c.*119G>A	3_prime_UTR	Exon 11 of 11	ENSP00000260947.4	Q99728-1
BARD1	ENST00000617164.5	TSL:1	c.*119G>A	3_prime_UTR	Exon 10 of 10	ENSP00000480470.1	Q99728-2
BARD1	ENST00000619009.5	TSL:1	c.*119G>A	3_prime_UTR	Exon 5 of 5	ENSP00000482293.1	A0A087WZ19

Frequencies

GnomAD3 genomes

AF:

0.000248

AC:

AN:

120766

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000927

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000853

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00298

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000174

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000452

AC:

235

AN:

520124

Hom.:

Cov.:

AF XY:

0.000482

AC XY:

127

AN XY:

263462

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000480

AC:

AN:

12492

American (AMR)

AF:

0.000559

AC:

AN:

12518

Ashkenazi Jewish (ASJ)

AF:

0.000233

AC:

AN:

12898

East Asian (EAS)

AF:

0.000369

AC:

AN:

24392

South Asian (SAS)

AF:

0.00143

AC:

AN:

27926

European-Finnish (FIN)

AF:

0.000482

AC:

AN:

22826

Middle Eastern (MID)

AF:

0.00111

AC:

AN:

2692

European-Non Finnish (NFE)

AF:

0.000367

AC:

139

AN:

378506

Other (OTH)

AF:

0.000657

AC:

AN:

25874

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.273

Heterozygous variant carriers

102

128

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000248

AC:

AN:

120806

Hom.:

Cov.:

AF XY:

0.000209

AC XY:

AN XY:

57358

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000925

AC:

AN:

32442

American (AMR)

AF:

0.0000852

AC:

AN:

11734

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3078

East Asian (EAS)

AF:

0.00

AC:

AN:

4180

South Asian (SAS)

AF:

0.00

AC:

AN:

3818

European-Finnish (FIN)

AF:

0.00298

AC:

AN:

5378

Middle Eastern (MID)

AF:

0.00

AC:

AN:

208

European-Non Finnish (NFE)

AF:

0.000174

AC:

AN:

57512

Other (OTH)

AF:

0.00

AC:

AN:

1672

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Familial cancer of breast (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.4

(source)

DANN

Benign

0.40

PhyloP100

-0.87

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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