Variant 2-85398769-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000263867.9(CAPG):c.680A>G(p.Lys227Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 1,604,810 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 30 hom. )

Consequence

CAPG
ENST00000263867.9 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.75

Variant links:

Genes affected

CAPG (HGNC:1474): (capping actin protein, gelsolin like) This gene encodes a member of the gelsolin/villin family of actin-regulatory proteins. The encoded protein reversibly blocks the barbed ends of F-actin filaments in a Ca2+ and phosphoinositide-regulated manner, but does not sever preformed actin filaments. By capping the barbed ends of actin filaments, the encoded protein contributes to the control of actin-based motility in non-muscle cells. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Jan 2012]

CAPG links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0039249063).

BP6

Variant 2-85398769-T-C is Benign according to our data. Variant chr2-85398769-T-C is described in ClinVar as [Benign]. Clinvar id is 731207.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00154 (235/152234) while in subpopulation EAS AF= 0.0425 (220/5174). AF 95% confidence interval is 0.0379. There are 3 homozygotes in gnomad4. There are 133 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAPG	NM_001747.4 linkuse as main transcript	c.680A>G	p.Lys227Arg	missense_variant	7/10	ENST00000263867.9	NP_001738.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAPG	ENST00000263867.9 linkuse as main transcript	c.680A>G	p.Lys227Arg	missense_variant	7/10	1	NM_001747.4	ENSP00000263867	P1	P40121-1

Frequencies

GnomAD3 genomes

AF:

0.00154

AC:

234

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0422

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00365

AC:

844

AN:

231328

Hom.:

AF XY:

0.00340

AC XY:

425

AN XY:

124894

show subpopulations

Gnomad AFR exome

AF:

0.0000688

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0470

Gnomad SAS exome

AF:

0.000529

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000289

Gnomad OTH exome

AF:

0.000703

GnomAD4 exome

AF:

0.00117

AC:

1698

AN:

1452576

Hom.:

Cov.:

AF XY:

0.00114

AC XY:

820

AN XY:

721490

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000231

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0379

Gnomad4 SAS exome

AF:

0.000806

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000235

Gnomad4 OTH exome

AF:

0.00177

GnomAD4 genome

AF:

0.00154

AC:

235

AN:

152234

Hom.:

Cov.:

AF XY:

0.00179

AC XY:

133

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0425

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00179

Hom.:

Bravo

AF:

0.00198

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00314

AC:

380

Asia WGS

AF:

0.00779

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

T;.;T;T;T;T;T

Eigen

Benign

0.16

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.80

.;T;.;T;.;.;T

MetaRNN

Benign

0.0039

T;T;T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.3

L;.;L;L;.;.;.

MutationTaster

Benign

0.50

D;N;N;N;N

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.8

N;N;N;N;N;N;N

REVEL

Benign

0.099

Sift

Benign

0.63

T;T;T;T;T;T;T

Sift4G

Benign

0.56

T;T;T;T;T;T;T

Polyphen

0.14

B;.;B;B;.;.;.

Vest4

0.24

MVP

0.65

MPC

0.10

ClinPred

0.040

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.084

gMVP

0.22

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