Genetic Variant BCAR1:p.Ala870Ser (chr16-75229516-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_014567.5(BCAR1):c.2608G>T(p.Ala870Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000212 in 1,414,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A870T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

BCAR1
NM_014567.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.97

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26717204).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014567.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BCAR1	NM_014567.5	MANE Select	c.2608G>T	p.Ala870Ser	missense	Exon 7 of 7	NP_055382.2
BCAR1	NM_001170714.3		c.2746G>T	p.Ala916Ser	missense	Exon 8 of 8	NP_001164185.1	P56945-6
BCAR1	NM_001170715.3		c.2662G>T	p.Ala888Ser	missense	Exon 7 of 7	NP_001164186.1	P56945-7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BCAR1	ENST00000162330.10	TSL:1 MANE Select	c.2608G>T	p.Ala870Ser	missense	Exon 7 of 7	ENSP00000162330.5	P56945-1
BCAR1	ENST00000563038.5	TSL:1	n.2213G>T		non_coding_transcript_exon	Exon 3 of 3
BCAR1	ENST00000418647.7	TSL:2	c.2746G>T	p.Ala916Ser	missense	Exon 8 of 8	ENSP00000391669.3	P56945-6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000212

AC:

AN:

1414868

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

698256

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32792

American (AMR)

AF:

0.00

AC:

AN:

41982

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24804

East Asian (EAS)

AF:

0.00

AC:

AN:

38450

South Asian (SAS)

AF:

0.00

AC:

AN:

81256

European-Finnish (FIN)

AF:

0.0000683

AC:

AN:

43952

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4750

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1088338

Other (OTH)

AF:

0.00

AC:

AN:

58544

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

Heterozygous variant carriers

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.043

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.027

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.020

MetaRNN

Benign

0.27

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.1

PhyloP100

2.0

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.50

REVEL

Benign

0.18

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.85

Vest4

0.29

MutPred

0.43

Gain of disorder (P = 0.0468)

MVP

0.53

MPC

0.46

ClinPred

0.90

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.64

gMVP

0.33

Mutation Taster

=86/14

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over