Variant 11-128968955-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0370

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 -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 GnomAd4 at 610 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP32	NM_001378024.1 linkuse as main transcript	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 linkuse as main transcript	c.6258C>T	p.Pro2086=	synonymous_variant	23/23		NM_001378024.1	P3

Frequencies

GnomAD3 genomes

AF:

0.00401

AC:

610

AN:

152168

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00347

AC XY:

418

AN XY:

120442

show subpopulations

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.:

Cov.:

AF XY:

0.00577

AC XY:

4009

AN XY:

695126

show subpopulations

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.:

Cov.:

AF XY:

0.00361

AC XY:

269

AN XY:

74442

show subpopulations

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.:

Bravo

AF:

0.00466

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	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, no assertion criteria provided

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

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