16-75234923-C-G

Variant names:

• chr16-75234923-C-G
• rs1232194704
• NM_014567.5:c.1976G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014567.5(BCAR1):​c.1976G>C​(p.Gly659Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000714 in 1,400,962 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: BCAR1 NM_014567.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.84
• Publications: 2 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCAR1	NM_014567.5	MANE Select	c.1976G>C	p.Gly659Ala	missense	Exon 5 of 7	NP_055382.2
	BCAR1	NM_001170714.3		c.2114G>C	p.Gly705Ala	missense	Exon 6 of 8	NP_001164185.1	P56945-6
	BCAR1	NM_001170715.3		c.2030G>C	p.Gly677Ala	missense	Exon 5 of 7	NP_001164186.1	P56945-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCAR1	ENST00000162330.10	TSL:1 MANE Select	c.1976G>C	p.Gly659Ala	missense	Exon 5 of 7	ENSP00000162330.5	P56945-1
	BCAR1	ENST00000563038.5	TSL:1	n.1581G>C		non_coding_transcript_exon	Exon 1 of 3
	BCAR1	ENST00000418647.7	TSL:2	c.2114G>C	p.Gly705Ala	missense	Exon 6 of 8	ENSP00000391669.3	P56945-6

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.00000473 AC: 1 AN: 211536 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000330

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.14e-7 AC: 1 AN: 1400962 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 687670

African (AFR) AF: 0.00 AC: 0 AN: 32412

American (AMR) AF: 0.0000250 AC: 1 AN: 40034

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22054

East Asian (EAS) AF: 0.00 AC: 0 AN: 39000

South Asian (SAS) AF: 0.00 AC: 0 AN: 76834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50752

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5462

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1076682

Other (OTH) AF: 0.00 AC: 0 AN: 57732

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.042	T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		5.8
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.18
Sift	Uncertain	0.010	D
Sift4G	Benign	0.089	T
Polyphen		1.0	D
Vest4		0.65
MutPred		0.099		Gain of catalytic residue at G659 (P = 0.1024)
MVP		0.55
MPC		0.51
ClinPred		0.84	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.34
Mutation Taster		=47/53	disease causing

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

Other links and lift over

dbSNP: rs1232194704; hg19: chr16-75268821;