11-128980409-A-G

Position:

• chr11-128980409-A-G

Variant summary

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

The NM_001378024.1(ARHGAP32):​c.1976+144T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 561,186 control chromosomes in the GnomAD database, including 25,815 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 0.28 (6284 hom., cov: 32)
  • Exomes 𝑓: 0.30 (19531 hom.)
• Consequence: ARHGAP32 NM_001378024.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.449

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP32	NM_001378024.1	c.1976+144T>C		intron_variant		ENST00000682385.1	NP_001364953.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP32	ENST00000682385.1	c.1976+144T>C		intron_variant			NM_001378024.1	ENSP00000507720	P3

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41913 AN: 152078 Hom.: 6283 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.322

GnomAD4 exome AF: 0.302 AC: 123312 AN: 408990 Hom.: 19531 AF XY: 0.298 AC XY: 63464 AN XY: 212800

Gnomad4 AFR exome AF: 0.183

Gnomad4 AMR exome AF: 0.360

Gnomad4 ASJ exome AF: 0.354

Gnomad4 EAS exome AF: 0.283

Gnomad4 SAS exome AF: 0.174

Gnomad4 FIN exome AF: 0.223

Gnomad4 NFE exome AF: 0.325

Gnomad4 OTH exome AF: 0.315

GnomAD4 genome AF: 0.275 AC: 41924 AN: 152196 Hom.: 6284 Cov.: 32 AF XY: 0.270 AC XY: 20066 AN XY: 74408

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.374

Gnomad4 EAS AF: 0.310

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.215

Gnomad4 NFE AF: 0.323

Gnomad4 OTH AF: 0.324

Alfa AF: 0.283 Hom.: 1036

Bravo AF: 0.287

Asia WGS AF: 0.210 AC: 730 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.8
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2276027; hg19: chr11-128850304;