16-75229987-G-C

Variant names:

• chr16-75229987-G-C
• rs373196130
• NM_014567.5:c.2137C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014567.5(BCAR1):​c.2137C>G​(p.Arg713Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000706 in 1,417,276 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: BCAR1 NM_014567.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.90

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35445637).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCAR1	NM_014567.5	c.2137C>G	p.Arg713Gly	missense_variant	Exon 7 of 7	ENST00000162330.10	NP_055382.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCAR1	ENST00000162330.10	c.2137C>G	p.Arg713Gly	missense_variant	Exon 7 of 7	1	NM_014567.5	ENSP00000162330.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.06e-7 AC: 1 AN: 1417276 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 699064

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.20e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	.;T;.;.;.;.;.;.
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.48	N
LIST_S2	Pathogenic	0.97	D;D;D;D;D;D;D;D
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.35	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	.;M;.;M;.;.;.;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.5	D;D;D;D;D;D;D;D
REVEL	Benign	0.19
Sift	Uncertain	0.0030	D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.0090	D;D;D;D;D;D;D;D
Polyphen		1.0	.;D;.;.;.;.;.;.
Vest4		0.50
MutPred		0.27		.;Loss of stability (P = 0.0422);.;Loss of stability (P = 0.0422);.;.;.;.;
MVP		0.59
MPC		0.56
ClinPred		0.98	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.50
gMVP		0.55

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

Other links and lift over

dbSNP: rs373196130; hg19: chr16-75263885;