16-75230007-C-G

Variant names:

• chr16-75230007-C-G
• rs376571253
• NM_014567.5:c.2117G>C

Variant summary

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

The NM_014567.5(BCAR1):​c.2117G>C​(p.Arg706Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000722 in 1,385,704 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R706Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: BCAR1 NM_014567.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.47
• Publications: 1 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.2117G>C	p.Arg706Pro	missense	Exon 7 of 7	NP_055382.2
	BCAR1	NM_001170714.3		c.2255G>C	p.Arg752Pro	missense	Exon 8 of 8	NP_001164185.1	P56945-6
	BCAR1	NM_001170715.3		c.2171G>C	p.Arg724Pro	missense	Exon 7 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.2117G>C	p.Arg706Pro	missense	Exon 7 of 7	ENSP00000162330.5	P56945-1
	BCAR1	ENST00000563038.5	TSL:1	n.1722G>C		non_coding_transcript_exon	Exon 3 of 3
	BCAR1	ENST00000418647.7	TSL:2	c.2255G>C	p.Arg752Pro	missense	Exon 8 of 8	ENSP00000391669.3	P56945-6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.22e-7 AC: 1 AN: 1385704 Hom.: 0 Cov.: 30 AF XY: 0.00000147 AC XY: 1 AN XY: 679562

African (AFR) AF: 0.00 AC: 0 AN: 31428

American (AMR) AF: 0.00 AC: 0 AN: 35422

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21394

East Asian (EAS) AF: 0.00 AC: 0 AN: 38860

South Asian (SAS) AF: 0.00 AC: 0 AN: 74000

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49512

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5404

European-Non Finnish (NFE) AF: 9.32e-7 AC: 1 AN: 1072576

Other (OTH) AF: 0.00 AC: 0 AN: 57108

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Uncertain	0.025	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.5
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.22
Sift	Benign	0.10	T
Sift4G	Benign	0.10	T
Polyphen		1.0	D
Vest4		0.70
MutPred		0.38		Gain of loop (P = 3e-04)
MVP		0.53
MPC		0.58
ClinPred		0.91	D
GERP RS		4.7
Varity_R		0.66
gMVP		0.71
Mutation Taster		=19/81	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: rs376571253; hg19: chr16-75263905;