11-129092775-T-G

Variant names:

• chr11-129092775-T-G
• rs10488729
• NM_001378024.1:c.531+846A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378024.1(ARHGAP32):​c.531+846A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 151,850 control chromosomes in the GnomAD database, including 3,091 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 0.20 (3091 hom., cov: 32)
• Consequence: ARHGAP32 NM_001378024.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP32	NM_001378024.1	c.531+846A>C		intron_variant	Intron 6 of 22	ENST00000682385.1	NP_001364953.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP32	ENST00000682385.1	c.531+846A>C		intron_variant	Intron 6 of 22		NM_001378024.1	ENSP00000507720.1
ARHGAP32	ENST00000310343.13	c.489+846A>C		intron_variant	Intron 5 of 21	1		ENSP00000310561.8
ARHGAP32	ENST00000524655.5	c.267+846A>C		intron_variant	Intron 4 of 18	1		ENSP00000432468.1
ARHGAP32	ENST00000525234.1	c.411+846A>C		intron_variant	Intron 6 of 6	3		ENSP00000432303.1

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29663 AN: 151732 Hom.: 3091 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.195 AC: 29676 AN: 151850 Hom.: 3091 Cov.: 32 AF XY: 0.199 AC XY: 14741 AN XY: 74206

African (AFR) AF: 0.160 AC: 6637 AN: 41488

American (AMR) AF: 0.126 AC: 1930 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 492 AN: 3464

East Asian (EAS) AF: 0.168 AC: 868 AN: 5164

South Asian (SAS) AF: 0.153 AC: 738 AN: 4826

European-Finnish (FIN) AF: 0.303 AC: 3204 AN: 10558

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.226 AC: 15335 AN: 67778

Other (OTH) AF: 0.158 AC: 333 AN: 2104

Alfa AF: 0.194 Hom.: 1780

Bravo AF: 0.181

Asia WGS AF: 0.146 AC: 511 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
DANN	Benign	0.74
PhyloP100		-1.5
Mutation Taster		=100/0	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: rs10488729; hg19: chr11-128962670; COSMIC: COSV59849043;