rs546239

Positions:

• chr11-128965863-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.*3044G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.885 in 152,228 control chromosomes in the GnomAD database, including 59,743 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 0.88 (59742 hom., cov: 31)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: ARHGAP32 NM_001378024.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.381

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.932 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP32	NM_001378024.1	c.*3044G>A		3_prime_UTR_variant	23/23	ENST00000682385.1	NP_001364953.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP32	ENST00000682385.1	c.*3044G>A		3_prime_UTR_variant	23/23		NM_001378024.1	ENSP00000507720	P3
ARHGAP32	ENST00000310343.13	c.*3044G>A		3_prime_UTR_variant	22/22	1		ENSP00000310561	A1

Frequencies

GnomAD3 genomes AF: 0.885 AC: 134556 AN: 152108 Hom.: 59703 Cov.: 31

Gnomad AFR AF: 0.940

Gnomad AMI AF: 0.923

Gnomad AMR AF: 0.858

Gnomad ASJ AF: 0.818

Gnomad EAS AF: 0.810

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.895

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.878

Gnomad OTH AF: 0.880

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

Gnomad4 FIN exome AF: 1.00

GnomAD4 genome AF: 0.885 AC: 134650 AN: 152226 Hom.: 59742 Cov.: 31 AF XY: 0.882 AC XY: 65606 AN XY: 74420

Gnomad4 AFR AF: 0.940

Gnomad4 AMR AF: 0.858

Gnomad4 ASJ AF: 0.818

Gnomad4 EAS AF: 0.809

Gnomad4 SAS AF: 0.683

Gnomad4 FIN AF: 0.895

Gnomad4 NFE AF: 0.878

Gnomad4 OTH AF: 0.876

Alfa AF: 0.884 Hom.: 15824

Bravo AF: 0.890

Asia WGS AF: 0.731 AC: 2546 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.38
DANN	Benign	0.71

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: rs546239; hg19: chr11-128835758;