Variant 11-128969631-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 1P and 14B. PP2BP4_StrongBP6_ModerateBA1

The NM_001378024.1(ARHGAP32):c.5582G>C(p.Ser1861Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0775 in 1,613,988 control chromosomes in the GnomAD database, including 5,307 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.093 ( 765 hom., cov: 32)

Exomes 𝑓: 0.076 ( 4542 hom. )

Consequence

ARHGAP32
NM_001378024.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.50

Variant links:

Genes affected

ARHGAP32 (HGNC:17399): (Rho GTPase activating protein 32) RICS is a neuron-associated GTPase-activating protein that may regulate dendritic spine morphology and strength by modulating Rho GTPase (see RHOA; MIM 165390) activity (Okabe et al., 2003 [PubMed 12531901]).[supplied by OMIM, Mar 2008]

ARHGAP32 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

PP2

Missense variant where missense usually causes diseases, ARHGAP32

BP4

Computational evidence support a benign effect (MetaRNN=0.001899302).

BP6

Variant 11-128969631-C-G is Benign according to our data. Variant chr11-128969631-C-G is described in ClinVar as [Benign]. Clinvar id is 3055483.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP32	NM_001378024.1 linkuse as main transcript	c.5582G>C	p.Ser1861Thr	missense_variant	23/23	ENST00000682385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP32	ENST00000682385.1 linkuse as main transcript	c.5582G>C	p.Ser1861Thr	missense_variant	23/23		NM_001378024.1	P3

Frequencies

GnomAD3 genomes

AF:

0.0930

AC:

14137

AN:

152092

Hom.:

765

Cov.:

show subpopulations

Gnomad AFR

AF:

0.128

Gnomad AMI

AF:

0.141

Gnomad AMR

AF:

0.0720

Gnomad ASJ

AF:

0.0671

Gnomad EAS

AF:

0.0532

Gnomad SAS

AF:

0.0275

Gnomad FIN

AF:

0.125

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0798

Gnomad OTH

AF:

0.0877

GnomAD3 exomes

AF:

0.0743

AC:

18664

AN:

251284

Hom.:

822

AF XY:

0.0724

AC XY:

9839

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.129

Gnomad AMR exome

AF:

0.0495

Gnomad ASJ exome

AF:

0.0721

Gnomad EAS exome

AF:

0.0516

Gnomad SAS exome

AF:

0.0297

Gnomad FIN exome

AF:

0.122

Gnomad NFE exome

AF:

0.0802

Gnomad OTH exome

AF:

0.0843

GnomAD4 exome

AF:

0.0759

AC:

110965

AN:

1461778

Hom.:

4542

Cov.:

AF XY:

0.0746

AC XY:

54227

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.133

Gnomad4 AMR exome

AF:

0.0525

Gnomad4 ASJ exome

AF:

0.0703

Gnomad4 EAS exome

AF:

0.0561

Gnomad4 SAS exome

AF:

0.0282

Gnomad4 FIN exome

AF:

0.126

Gnomad4 NFE exome

AF:

0.0770

Gnomad4 OTH exome

AF:

0.0822

GnomAD4 genome

AF:

0.0930

AC:

14150

AN:

152210

Hom.:

765

Cov.:

AF XY:

0.0929

AC XY:

6912

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.128

Gnomad4 AMR

AF:

0.0720

Gnomad4 ASJ

AF:

0.0671

Gnomad4 EAS

AF:

0.0535

Gnomad4 SAS

AF:

0.0269

Gnomad4 FIN

AF:

0.125

Gnomad4 NFE

AF:

0.0798

Gnomad4 OTH

AF:

0.0868

Alfa

AF:

0.0821

Hom.:

405

Bravo

AF:

0.0921

TwinsUK

AF:

0.0812

AC:

301

ALSPAC

AF:

0.0773

AC:

298

ESP6500AA

AF:

0.120

AC:

529

ESP6500EA

AF:

0.0763

AC:

656

ExAC

AF:

0.0747

AC:

9067

Asia WGS

AF:

0.0480

AC:

169

AN:

3478

EpiCase

AF:

0.0791

EpiControl

AF:

0.0858

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ARHGAP32-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 17, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.69

CADD

Benign

1.0

DANN

Benign

0.89

DEOGEN2

Benign

0.097

T;.;.

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.82

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.77

T;.;T

MetaRNN

Benign

0.0019

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;.;.

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.18

N;N;N

REVEL

Benign

0.11

Sift

Uncertain

0.0040

D;D;D

Sift4G

Uncertain

0.037

D;D;D

Polyphen

0.039

B;.;.

Vest4

0.070

MPC

0.12

ClinPred

0.010

GERP RS

0.31

Varity_R

0.090

gMVP

0.11

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