11-129249401-C-T

Variant names:

• chr11-129249401-C-T
• rs4129583
• NM_001378025.1:c.-5+30022G>A

Variant summary

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

The NM_001378025.1(ARHGAP32):​c.-5+30022G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 151,976 control chromosomes in the GnomAD database, including 3,259 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 (3259 hom., cov: 32)
• Consequence: ARHGAP32 NM_001378025.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.803
• Publications: 0 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]

ENSG00000293970 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP32	NM_001378025.1	c.-5+30022G>A		intron_variant	Intron 1 of 21		NP_001364954.1
LOC399975	NR_145484.1	n.140-12153G>A		intron_variant	Intron 1 of 1
ARHGAP32	XM_011543072.3	c.-5+17466G>A		intron_variant	Intron 1 of 22		XP_011541374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP32	ENST00000525234.1	c.-5+29745G>A		intron_variant	Intron 1 of 6	3		ENSP00000432303.1
ENSG00000293970	ENST00000720279.1	n.179-12153G>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30622 AN: 151858 Hom.: 3264 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.202 AC: 30632 AN: 151976 Hom.: 3259 Cov.: 32 AF XY: 0.206 AC XY: 15310 AN XY: 74288

African (AFR) AF: 0.165 AC: 6841 AN: 41446

American (AMR) AF: 0.128 AC: 1949 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 482 AN: 3466

East Asian (EAS) AF: 0.279 AC: 1443 AN: 5174

South Asian (SAS) AF: 0.209 AC: 1005 AN: 4808

European-Finnish (FIN) AF: 0.300 AC: 3168 AN: 10550

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.225 AC: 15263 AN: 67942

Other (OTH) AF: 0.163 AC: 343 AN: 2110

Alfa AF: 0.213 Hom.: 1065

Bravo AF: 0.187

Asia WGS AF: 0.209 AC: 729 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.6
DANN	Benign	0.41
PhyloP100		-0.80

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4129583; hg19: chr11-129119296;