Genetic Variant NM_001378024.1:c.3528A>G (chr11-128972978-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001378024.1(ARHGAP32):c.3528A>G(p.Glu1176Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 1,613,742 control chromosomes in the GnomAD database, including 21,726 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.19 ( 3006 hom., cov: 31)

Exomes 𝑓: 0.16 ( 18720 hom. )

Consequence

ARHGAP32
NM_001378024.1 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.652

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 11-128972978-T-C is Benign according to our data. Variant chr11-128972978-T-C is described in ClinVar as [Benign]. Clinvar id is 3060336.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.652 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP32	NM_001378024.1 link	c.3528A>G	p.Glu1176Glu	synonymous_variant	Exon 22 of 23	ENST00000682385.1	NP_001364953.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP32	ENST00000682385.1 link	c.3528A>G	p.Glu1176Glu	synonymous_variant	Exon 22 of 23		NM_001378024.1	ENSP00000507720.1		A0A804HK06

Frequencies

GnomAD3 genomes

AF:

0.190

AC:

28788

AN:

151820

Hom.:

3002

Cov.:

show subpopulations

Gnomad AFR

AF:

0.280

Gnomad AMI

AF:

0.0965

Gnomad AMR

AF:

0.204

Gnomad ASJ

AF:

0.116

Gnomad EAS

AF:

0.171

Gnomad SAS

AF:

0.195

Gnomad FIN

AF:

0.149

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.144

Gnomad OTH

AF:

0.196

GnomAD3 exomes

AF:

0.176

AC:

44168

AN:

251482

Hom.:

4227

AF XY:

0.173

AC XY:

23469

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.284

Gnomad AMR exome

AF:

0.247

Gnomad ASJ exome

AF:

0.113

Gnomad EAS exome

AF:

0.161

Gnomad SAS exome

AF:

0.199

Gnomad FIN exome

AF:

0.147

Gnomad NFE exome

AF:

0.147

Gnomad OTH exome

AF:

0.153

GnomAD4 exome

AF:

0.156

AC:

228191

AN:

1461804

Hom.:

18720

Cov.:

AF XY:

0.156

AC XY:

113703

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.284

Gnomad4 AMR exome

AF:

0.239

Gnomad4 ASJ exome

AF:

0.119

Gnomad4 EAS exome

AF:

0.166

Gnomad4 SAS exome

AF:

0.196

Gnomad4 FIN exome

AF:

0.147

Gnomad4 NFE exome

AF:

0.147

Gnomad4 OTH exome

AF:

0.159

GnomAD4 genome

AF:

0.190

AC:

28828

AN:

151938

Hom.:

3006

Cov.:

AF XY:

0.189

AC XY:

14070

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.280

Gnomad4 AMR

AF:

0.205

Gnomad4 ASJ

AF:

0.116

Gnomad4 EAS

AF:

0.171

Gnomad4 SAS

AF:

0.194

Gnomad4 FIN

AF:

0.149

Gnomad4 NFE

AF:

0.144

Gnomad4 OTH

AF:

0.195

Alfa

AF:

0.154

Hom.:

3198

Bravo

AF:

0.200

Asia WGS

AF:

0.187

AC:

652

AN:

3478

EpiCase

AF:

0.140

EpiControl

AF:

0.147

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ARHGAP32-related disorder

Benign:1

Oct 22, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.2

DANN

Benign

0.56

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