rs2276027

Variant names:

• chr11-128980409-A-G
• rs2276027
• NM_001378024.1:c.1976+144T>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.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
• 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=-0.8).
• 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 rank	MANE	Protein	UniProt
ARHGAP32	NM_001378024.1	c.1976+144T>C		intron_variant	Intron 18 of 22	ENST00000682385.1	NP_001364953.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP32	ENST00000682385.1	c.1976+144T>C		intron_variant	Intron 18 of 22		NM_001378024.1	ENSP00000507720.1

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

African (AFR) AF: 0.183 AC: 1923 AN: 10500

American (AMR) AF: 0.360 AC: 4774 AN: 13262

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 4319 AN: 12210

East Asian (EAS) AF: 0.283 AC: 7860 AN: 27764

South Asian (SAS) AF: 0.174 AC: 5201 AN: 29830

European-Finnish (FIN) AF: 0.223 AC: 6843 AN: 30620

Middle Eastern (MID) AF: 0.376 AC: 672 AN: 1788

European-Non Finnish (NFE) AF: 0.325 AC: 84282 AN: 259368

Other (OTH) AF: 0.315 AC: 7438 AN: 23648

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

African (AFR) AF: 0.181 AC: 7507 AN: 41522

American (AMR) AF: 0.352 AC: 5382 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1299 AN: 3472

East Asian (EAS) AF: 0.310 AC: 1609 AN: 5186

South Asian (SAS) AF: 0.166 AC: 800 AN: 4828

European-Finnish (FIN) AF: 0.215 AC: 2277 AN: 10596

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.323 AC: 21991 AN: 68000

Other (OTH) AF: 0.324 AC: 685 AN: 2116

Alfa AF: 0.280 Hom.: 1049

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
PhyloP100		0.45
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2276027; hg19: chr11-128850304;