11-128968955-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001378024.1(ARHGAP32):c.6258C>T(p.Pro2086=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00565 in 1,564,532 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0040 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0058 (35 hom.)
• Consequence: ARHGAP32 NM_001378024.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0370

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 11-128968955-G-A is Benign according to our data. Variant chr11-128968955-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 713706.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.037 with no splicing effect.
• BS2: High AC in GnomAd at 610 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP32	NM_001378024.1	c.6258C>T	p.Pro2086=	synonymous_variant	23/23	ENST00000682385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP32	ENST00000682385.1	c.6258C>T	p.Pro2086=	synonymous_variant	23/23		NM_001378024.1	P3

Frequencies

GnomAD3 genomes AF: 0.00401 AC: 610 AN: 152168 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00142

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00746

Gnomad ASJ AF: 0.0135

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000753

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00535

Gnomad OTH AF: 0.00672

GnomAD3 exomes AF: 0.00362 AC: 812 AN: 224020 Hom.: 4 AF XY: 0.00347 AC XY: 418 AN XY: 120442

Gnomad AFR exome AF: 0.00155

Gnomad AMR exome AF: 0.00323

Gnomad ASJ exome AF: 0.0131

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000405

Gnomad FIN exome AF: 0.00101

Gnomad NFE exome AF: 0.00525

Gnomad OTH exome AF: 0.00513

GnomAD4 exome AF: 0.00583 AC: 8235 AN: 1412246 Hom.: 35 Cov.: 30 AF XY: 0.00577 AC XY: 4009 AN XY: 695126

Gnomad4 AFR exome AF: 0.00115

Gnomad4 AMR exome AF: 0.00395

Gnomad4 ASJ exome AF: 0.0124

Gnomad4 EAS exome AF: 0.0000515

Gnomad4 SAS exome AF: 0.0000376

Gnomad4 FIN exome AF: 0.00142

Gnomad4 NFE exome AF: 0.00680

Gnomad4 OTH exome AF: 0.00512

GnomAD4 genome AF: 0.00401 AC: 610 AN: 152286 Hom.: 1 Cov.: 32 AF XY: 0.00361 AC XY: 269 AN XY: 74442

Gnomad4 AFR AF: 0.00142

Gnomad4 AMR AF: 0.00745

Gnomad4 ASJ AF: 0.0135

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.000753

Gnomad4 NFE AF: 0.00535

Gnomad4 OTH AF: 0.00665

Alfa AF: 0.00396 Hom.: 0

Bravo AF: 0.00466

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2022	ARHGAP32: BP4, BP7 -

ARHGAP32-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 20, 2019

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	-0.53
Cadd	Benign	7.6
Dann	Benign	0.61

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: rs116891747; hg19: chr11-128838850;