rs10893947

Positions:

• chr11-129000529-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378024.1(ARHGAP32):​c.1046-2061G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 151,954 control chromosomes in the GnomAD database, including 4,365 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (4365 hom., cov: 32)
• Consequence: ARHGAP32 NM_001378024.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.634

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP32	NM_001378024.1	c.1046-2061G>A		intron_variant		ENST00000682385.1	NP_001364953.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP32	ENST00000682385.1	c.1046-2061G>A		intron_variant			NM_001378024.1	ENSP00000507720	P3

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35565 AN: 151836 Hom.: 4360 Cov.: 32

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.206

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.234 AC: 35592 AN: 151954 Hom.: 4365 Cov.: 32 AF XY: 0.241 AC XY: 17906 AN XY: 74266

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.336

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.326

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.203

Alfa AF: 0.241 Hom.: 562

Bravo AF: 0.226

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.8
DANN	Benign	0.41

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: rs10893947; hg19: chr11-128870424;