Variant 1-40069786-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_006367.4(CAP1):c.905C>T(p.Ala302Val) variant causes a missense change. The variant allele was found at a frequency of 0.000414 in 1,612,322 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00051 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00040 ( 1 hom. )

Consequence

CAP1
NM_006367.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.45

Variant links:

Genes affected

CAP1 (HGNC:20040): (cyclase associated actin cytoskeleton regulatory protein 1) The protein encoded by this gene is related to the S. cerevisiae CAP protein, which is involved in the cyclic AMP pathway. The human protein is able to interact with other molecules of the same protein, as well as with CAP2 and actin. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2016]

CAP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.038006812).

BS2

High AC in GnomAd4 at 77 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAP1	NM_006367.4 linkuse as main transcript	c.905C>T	p.Ala302Val	missense_variant	9/13	ENST00000372805.8	NP_006358.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAP1	ENST00000372805.8 linkuse as main transcript	c.905C>T	p.Ala302Val	missense_variant	9/13	1	NM_006367.4	ENSP00000361891	P3	Q01518-1

Frequencies

GnomAD3 genomes

AF:

0.000506

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.000566

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000519

AC:

128

AN:

246756

Hom.:

AF XY:

0.000627

AC XY:

AN XY:

133896

show subpopulations

Gnomad AFR exome

AF:

0.0000647

Gnomad AMR exome

AF:

0.000706

Gnomad ASJ exome

AF:

0.000404

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000892

Gnomad FIN exome

AF:

0.000605

Gnomad NFE exome

AF:

0.000483

Gnomad OTH exome

AF:

0.000837

GnomAD4 exome

AF:

0.000404

AC:

590

AN:

1460068

Hom.:

Cov.:

AF XY:

0.000441

AC XY:

320

AN XY:

726356

show subpopulations

Gnomad4 AFR exome

AF:

0.000270

Gnomad4 AMR exome

AF:

0.000903

Gnomad4 ASJ exome

AF:

0.000307

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000849

Gnomad4 FIN exome

AF:

0.000356

Gnomad4 NFE exome

AF:

0.000316

Gnomad4 OTH exome

AF:

0.000829

GnomAD4 genome

AF:

0.000506

AC:

AN:

152254

Hom.:

Cov.:

AF XY:

0.000497

AC XY:

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.000566

Gnomad4 NFE

AF:

0.000456

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000491

Hom.:

Bravo

AF:

0.000536

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000484

AC:

ExAC

AF:

0.000480

AC:

EpiCase

AF:

0.000600

EpiControl

AF:

0.000594

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 22, 2022

The c.905C>T (p.A302V) alteration is located in exon 9 (coding exon 8) of the CAP1 gene. This alteration results from a C to T substitution at nucleotide position 905, causing the alanine (A) at amino acid position 302 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.068

T;.;T;.;.;T

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.77

.;.;.;.;T;T

M_CAP

Benign

0.0063

MetaRNN

Benign

0.038

T;T;T;T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.3

M;.;M;.;.;M

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-2.0

N;N;N;N;N;N

REVEL

Benign

0.10

Sift

Uncertain

0.010

D;D;D;D;D;D

Sift4G

Uncertain

0.050

T;D;T;D;D;T

Polyphen

0.84

P;.;P;.;.;P

Vest4

0.20

MVP

0.35

MPC

0.34

ClinPred

0.061

GERP RS

5.6

Varity_R

0.27

gMVP

0.35

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over