Genetic Variant NM_014567.5:c.2100+10C>T (chr16-75233836-G-A) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -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 Likely 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/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.641

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: Benign. The variant received -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/Likely_benign. ClinVar VariationId is 774924.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 391 AD gene.

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	Effect	Exon Rank	Protein	UniProt
BCAR1	NM_014567.5	MANE Select	c.2100+10C>T	intron	N/A	NP_055382.2
BCAR1	NM_001170714.3		c.2238+10C>T	intron	N/A	NP_001164185.1	P56945-6
BCAR1	NM_001170715.3		c.2154+10C>T	intron	N/A	NP_001164186.1	P56945-7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BCAR1	ENST00000162330.10	TSL:1 MANE Select	c.2100+10C>T	intron	N/A	ENSP00000162330.5	P56945-1
BCAR1	ENST00000563038.5	TSL:1	n.1705+10C>T	intron	N/A
BCAR1	ENST00000418647.7	TSL:2	c.2238+10C>T	intron	N/A	ENSP00000391669.3	P56945-6

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

GnomAD2 exomes

AF:

0.00184

AC:

408

AN:

221264

AF XY:

0.00158

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 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

African (AFR)

AF:

0.00476

AC:

158

AN:

33184

American (AMR)

AF:

0.00424

AC:

179

AN:

42264

Ashkenazi Jewish (ASJ)

AF:

0.00741

AC:

190

AN:

25636

East Asian (EAS)

AF:

0.0000514

AC:

AN:

38932

South Asian (SAS)

AF:

0.0000599

AC:

AN:

83518

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50864

Middle Eastern (MID)

AF:

0.00849

AC:

AN:

5656

European-Non Finnish (NFE)

AF:

0.000922

AC:

1017

AN:

1103186

Other (OTH)

AF:

0.00329

AC:

196

AN:

59650

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

178

266

355

444

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

152

190

<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

AF:

0.00257

AC:

391

AN:

152216

Hom.:

Cov.:

AF XY:

0.00249

AC XY:

185

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.00436

AC:

181

AN:

41538

American (AMR)

AF:

0.00536

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00807

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000208

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00119

AC:

AN:

67996

Other (OTH)

AF:

0.00712

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

102

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.000999

Hom.:

Bravo

AF:

0.00337

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.24

(source)

DANN

Benign

0.81

PhyloP100

-0.64

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over