11-128969261-T-C

Variant names:

• chr11-128969261-T-C
• rs3740829
• NM_001378024.1:c.5952A>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.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
• Publications: 9 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=-0.9).
• BP6: Variant 11-128969261-T-C is Benign according to our data. Variant chr11-128969261-T-C is described in ClinVar as Benign. ClinVar VariationId 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

GnomAD2 exomes AF: 0.0703 AC: 17665 AN: 251366 AF XY: 0.0691

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 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

African (AFR) AF: 0.0929 AC: 3111 AN: 33476

American (AMR) AF: 0.0459 AC: 2052 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0643 AC: 1681 AN: 26126

East Asian (EAS) AF: 0.0564 AC: 2237 AN: 39696

South Asian (SAS) AF: 0.0285 AC: 2455 AN: 86254

European-Finnish (FIN) AF: 0.126 AC: 6709 AN: 53414

Middle Eastern (MID) AF: 0.0570 AC: 329 AN: 5768

European-Non Finnish (NFE) AF: 0.0764 AC: 84948 AN: 1111962

Other (OTH) AF: 0.0777 AC: 4692 AN: 60390

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

African (AFR) AF: 0.0921 AC: 3826 AN: 41560

American (AMR) AF: 0.0607 AC: 930 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0602 AC: 209 AN: 3470

East Asian (EAS) AF: 0.0544 AC: 282 AN: 5182

South Asian (SAS) AF: 0.0269 AC: 130 AN: 4824

European-Finnish (FIN) AF: 0.125 AC: 1329 AN: 10614

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0790 AC: 5372 AN: 68024

Other (OTH) AF: 0.0738 AC: 156 AN: 2114

Alfa AF: 0.0776 Hom.: 915

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
PhyloP100		-1.4
Mutation Taster		=97/3	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: rs3740829; hg19: chr11-128839156;