rs581258

Variant names:

• chr11-128972978-T-C
• rs581258
• NM_001378024.1:c.3528A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

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
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.652
• Publications: 16 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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	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	c.3528A>G	p.Glu1176Glu	synonymous_variant	Exon 22 of 23		NM_001378024.1	ENSP00000507720.1

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28788 AN: 151820 Hom.: 3002 Cov.: 31

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

GnomAD2 exomes AF: 0.176 AC: 44168 AN: 251482 AF XY: 0.173

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 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.: 33 AF XY: 0.156 AC XY: 113703 AN XY: 727216

African (AFR) AF: 0.284 AC: 9504 AN: 33474

American (AMR) AF: 0.239 AC: 10703 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 3112 AN: 26136

East Asian (EAS) AF: 0.166 AC: 6595 AN: 39700

South Asian (SAS) AF: 0.196 AC: 16929 AN: 86258

European-Finnish (FIN) AF: 0.147 AC: 7841 AN: 53420

Middle Eastern (MID) AF: 0.131 AC: 755 AN: 5768

European-Non Finnish (NFE) AF: 0.147 AC: 163160 AN: 1111932

Other (OTH) AF: 0.159 AC: 9592 AN: 60392

GnomAD4 genome AF: 0.190 AC: 28828 AN: 151938 Hom.: 3006 Cov.: 31 AF XY: 0.189 AC XY: 14070 AN XY: 74266

African (AFR) AF: 0.280 AC: 11592 AN: 41426

American (AMR) AF: 0.205 AC: 3128 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 402 AN: 3470

East Asian (EAS) AF: 0.171 AC: 877 AN: 5140

South Asian (SAS) AF: 0.194 AC: 937 AN: 4826

European-Finnish (FIN) AF: 0.149 AC: 1572 AN: 10536

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9796 AN: 67986

Other (OTH) AF: 0.195 AC: 410 AN: 2104

Alfa AF: 0.158 Hom.: 4068

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

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
PhyloP100		-0.65
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs581258; hg19: chr11-128842873; COSMIC: COSV59849438;