11-128969261-T-C

Variant names:

• chr11-128969261-T-C
• rs3740829
• NM_001378024.1:c.5952A>G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001378024.1(ARHGAP32):​c.5952A>G​(p.Glu1984Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0747 in 1,614,106 control chromosomes in the GnomAD database, including 4,837 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.081 (563 hom., cov: 32)
  • Exomes 𝑓: 0.074 (4274 hom.)
• Consequence: ARHGAP32 NM_001378024.1 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.43

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 11-128969261-T-C is Benign according to our data. Variant chr11-128969261-T-C is described in ClinVar as [Benign]. Clinvar id is 3055563.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-1.43 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP32	NM_001378024.1	c.5952A>G	p.Glu1984Glu	synonymous_variant	Exon 23 of 23	ENST00000682385.1	NP_001364953.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP32	ENST00000682385.1	c.5952A>G	p.Glu1984Glu	synonymous_variant	Exon 23 of 23		NM_001378024.1	ENSP00000507720.1

Frequencies

GnomAD3 genomes AF: 0.0813 AC: 12376 AN: 152184 Hom.: 563 Cov.: 32

Gnomad AFR AF: 0.0920

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.0608

Gnomad ASJ AF: 0.0602

Gnomad EAS AF: 0.0541

Gnomad SAS AF: 0.0275

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0790

Gnomad OTH AF: 0.0746

GnomAD3 exomes AF: 0.0703 AC: 17665 AN: 251366 Hom.: 723 AF XY: 0.0691 AC XY: 9381 AN XY: 135852

Gnomad AFR exome AF: 0.0924

Gnomad AMR exome AF: 0.0432

Gnomad ASJ exome AF: 0.0647

Gnomad EAS exome AF: 0.0525

Gnomad SAS exome AF: 0.0299

Gnomad FIN exome AF: 0.122

Gnomad NFE exome AF: 0.0792

Gnomad OTH exome AF: 0.0794

GnomAD4 exome AF: 0.0740 AC: 108214 AN: 1461804 Hom.: 4274 Cov.: 31 AF XY: 0.0728 AC XY: 52977 AN XY: 727208

Gnomad4 AFR exome AF: 0.0929

Gnomad4 AMR exome AF: 0.0459

Gnomad4 ASJ exome AF: 0.0643

Gnomad4 EAS exome AF: 0.0564

Gnomad4 SAS exome AF: 0.0285

Gnomad4 FIN exome AF: 0.126

Gnomad4 NFE exome AF: 0.0764

Gnomad4 OTH exome AF: 0.0777

GnomAD4 genome AF: 0.0813 AC: 12386 AN: 152302 Hom.: 563 Cov.: 32 AF XY: 0.0819 AC XY: 6103 AN XY: 74488

Gnomad4 AFR AF: 0.0921

Gnomad4 AMR AF: 0.0607

Gnomad4 ASJ AF: 0.0602

Gnomad4 EAS AF: 0.0544

Gnomad4 SAS AF: 0.0269

Gnomad4 FIN AF: 0.125

Gnomad4 NFE AF: 0.0790

Gnomad4 OTH AF: 0.0738

Alfa AF: 0.0778 Hom.: 751

Bravo AF: 0.0779

Asia WGS AF: 0.0460 AC: 163 AN: 3478

EpiCase AF: 0.0773

EpiControl AF: 0.0840

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

ARHGAP32-related disorder Benign:1

Jan 17, 2020

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	-0.90
CADD	Benign	1.1
DANN	Benign	0.51

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

Other links and lift over

dbSNP: rs3740829; hg19: chr11-128839156;