Variant 15-32629654-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_014783.6(ARHGAP11A):c.997G>C(p.Asp333His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00721 in 1,613,496 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0048 ( 0 hom., cov: 27)

Exomes 𝑓: 0.0075 ( 62 hom. )

Consequence

ARHGAP11A
NM_014783.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 9.04

Variant links:

Genes affected

ARHGAP11A (HGNC:15783): (Rho GTPase activating protein 11A) This gene encodes a member of the Rho GTPase activating protein family. In response to DNA damage, the encoded protein interacts with the p53 tumor suppressor protein and stimulates its tetramerization, which results in cell-cycle arrest and apoptosis. A chromosomal deletion that includes this gene is one cause of Prader-Willi syndrome, and an intronic variant of this gene may be associated with sleep duration in children. This gene is highly expressed in colon cancers and in a human basal-like breast cancer cell line. This gene also produces a ARHGAP11A-SCG5 readthrough transcript and ARHGAP11A-SCG5 protein. [provided by RefSeq, Feb 2019]

ARHGAP11A links:

ARHGAP11A-SCG5 (HGNC:):

ARHGAP11A-SCG5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009388179).

BP6

Variant 15-32629654-G-C is Benign according to our data. Variant chr15-32629654-G-C is described in ClinVar as [Benign]. Clinvar id is 784682.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 62 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP11A	NM_014783.6 linkuse as main transcript	c.997G>C	p.Asp333His	missense_variant	8/12	ENST00000361627.8	NP_055598.1
ARHGAP11A-SCG5	NM_001368319.1 linkuse as main transcript	c.997G>C	p.Asp333His	missense_variant	8/14		NP_001355248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP11A	ENST00000361627.8 linkuse as main transcript	c.997G>C	p.Asp333His	missense_variant	8/12	1	NM_014783.6	ENSP00000355090	P1	Q6P4F7-1
	ENST00000647892.1 linkuse as main transcript	n.575-2738C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00477

AC:

725

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.0198

Gnomad AMR

AF:

0.00491

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00273

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00792

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00504

AC:

1264

AN:

250620

Hom.:

AF XY:

0.00517

AC XY:

700

AN XY:

135460

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.00293

Gnomad ASJ exome

AF:

0.000794

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00207

Gnomad FIN exome

AF:

0.00263

Gnomad NFE exome

AF:

0.00865

Gnomad OTH exome

AF:

0.00491

GnomAD4 exome

AF:

0.00746

AC:

10907

AN:

1461230

Hom.:

Cov.:

AF XY:

0.00729

AC XY:

5301

AN XY:

726904

show subpopulations

Gnomad4 AFR exome

AF:

0.00146

Gnomad4 AMR exome

AF:

0.00289

Gnomad4 ASJ exome

AF:

0.000651

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00194

Gnomad4 FIN exome

AF:

0.00341

Gnomad4 NFE exome

AF:

0.00903

Gnomad4 OTH exome

AF:

0.00527

GnomAD4 genome

AF:

0.00476

AC:

725

AN:

152266

Hom.:

Cov.:

AF XY:

0.00447

AC XY:

333

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.00118

Gnomad4 AMR

AF:

0.00491

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00273

Gnomad4 NFE

AF:

0.00792

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00675

Hom.:

Bravo

AF:

0.00467

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00628

AC:

ExAC

AF:

0.00524

AC:

636

EpiCase

AF:

0.00770

EpiControl

AF:

0.00866

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

Oct 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Uncertain

-0.030

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

.;T;.;.;.

Eigen

Pathogenic

0.83

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.82

.;T;D;.;T

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.0094

T;T;T;T;T

MetaSVM

Uncertain

0.73

MutationAssessor

Uncertain

2.3

.;M;M;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.6

D;D;D;D;D

REVEL

Uncertain

0.57

Sift

Uncertain

0.0020

D;D;D;D;D

Sift4G

Uncertain

0.0050

D;D;D;D;D

Polyphen

1.0

.;D;.;.;.

Vest4

0.44

MVP

0.95

MPC

0.24

ClinPred

0.016

GERP RS

5.4

Varity_R

0.37

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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