Genetic Variant BCAR1:c.2100+10C>T (chr16-75233836-G-A) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_014567.5(BCAR1):c.2100+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 1,595,106 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0026 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 8 hom. )

Consequence

BCAR1
NM_014567.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.641

Variant links:

Genes affected

BCAR1 (HGNC:971): (BCAR1 scaffold protein, Cas family member) The protein encoded by this gene is a member of the Crk-associated substrate (CAS) family of scaffold proteins, characterized by the presence of multiple protein-protein interaction domains and many serine and tyrosine phosphorylation sites. The encoded protein contains a Src-homology 3 (SH3) domain, a proline-rich domain, a substrate domain which contains 15 repeat of the YxxP consensus phosphorylation motif for Src family kinases, a serine-rich domain, and a bipartite Src-binding domain, which can bind both SH2 and SH3 domains. This adaptor protein functions in multiple cellular pathways, including in cell motility, apoptosis and cell cycle control. Dysregulation of this gene can have a wide range of effects, affecting different pathways, including cardiac development, vascular smooth muscle cells, liver and kidney function, endothelial migration, and cancer. [provided by RefSeq, Sep 2017]

BCAR1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 16-75233836-G-A is Benign according to our data. Variant chr16-75233836-G-A is described in ClinVar as [Benign]. Clinvar id is 774924.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-75233836-G-A is described in Lovd as [Benign].

BS2

High AC in GnomAd4 at 391 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCAR1	NM_014567.5 link	c.2100+10C>T		intron_variant	Intron 6 of 6	ENST00000162330.10	NP_055382.2	P56945-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCAR1	ENST00000162330.10 link	c.2100+10C>T		intron_variant	Intron 6 of 6	1	NM_014567.5	ENSP00000162330.5		P56945-1

Frequencies

GnomAD3 genomes

AF:

0.00255

AC:

388

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00430

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00537

Gnomad ASJ

AF:

0.00807

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00119

Gnomad OTH

AF:

0.00719

GnomAD3 exomes

AF:

0.00184

AC:

408

AN:

221264

Hom.:

AF XY:

0.00158

AC XY:

189

AN XY:

119944

show subpopulations

Gnomad AFR exome

AF:

0.00543

Gnomad AMR exome

AF:

0.00400

Gnomad ASJ exome

AF:

0.00792

Gnomad EAS exome

AF:

0.0000598

Gnomad SAS exome

AF:

0.0000363

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00117

Gnomad OTH exome

AF:

0.00305

GnomAD4 exome

AF:

0.00124

AC:

1795

AN:

1442890

Hom.:

Cov.:

AF XY:

0.00118

AC XY:

848

AN XY:

716236

show subpopulations

Gnomad4 AFR exome

AF:

0.00476

Gnomad4 AMR exome

AF:

0.00424

Gnomad4 ASJ exome

AF:

0.00741

Gnomad4 EAS exome

AF:

0.0000514

Gnomad4 SAS exome

AF:

0.0000599

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000922

Gnomad4 OTH exome

AF:

0.00329

GnomAD4 genome

AF:

0.00257

AC:

391

AN:

152216

Hom.:

Cov.:

AF XY:

0.00249

AC XY:

185

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.00436

Gnomad4 AMR

AF:

0.00536

Gnomad4 ASJ

AF:

0.00807

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00119

Gnomad4 OTH

AF:

0.00712

Alfa

AF:

0.000999

Hom.:

Bravo

AF:

0.00337

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 23, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.24

DANN

Benign

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over