chr11-129012984-G-C

Variant names:

• chr11-129012984-G-C
• rs493172
• NM_001378024.1:c.1046-14516C>G

Variant summary

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

The NM_001378024.1(ARHGAP32):​c.1046-14516C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,188 control chromosomes in the GnomAD database, including 1,589 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 0.14 (1589 hom., cov: 32)
• Consequence: ARHGAP32 NM_001378024.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.147
• Publications: 2 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378024.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP32	NM_001378024.1	MANE Select	c.1046-14516C>G		intron	N/A	NP_001364953.1
	ARHGAP32	NM_001142685.2		c.1004-14516C>G		intron	N/A	NP_001136157.1
	ARHGAP32	NM_001378025.1		c.884-14516C>G		intron	N/A	NP_001364954.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP32	ENST00000682385.1	MANE Select	c.1046-14516C>G		intron	N/A	ENSP00000507720.1
	ARHGAP32	ENST00000310343.13	TSL:1	c.1004-14516C>G		intron	N/A	ENSP00000310561.8
	ARHGAP32	ENST00000392657.7	TSL:1	c.-45+10875C>G		intron	N/A	ENSP00000376425.3

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21278 AN: 152070 Hom.: 1585 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.140 AC: 21287 AN: 152188 Hom.: 1589 Cov.: 32 AF XY: 0.140 AC XY: 10386 AN XY: 74408

African (AFR) AF: 0.122 AC: 5081 AN: 41528

American (AMR) AF: 0.127 AC: 1933 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 402 AN: 3472

East Asian (EAS) AF: 0.105 AC: 544 AN: 5184

South Asian (SAS) AF: 0.134 AC: 648 AN: 4820

European-Finnish (FIN) AF: 0.149 AC: 1575 AN: 10590

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10535 AN: 68004

Other (OTH) AF: 0.127 AC: 268 AN: 2114

Alfa AF: 0.0842 Hom.: 118

Bravo AF: 0.136

Asia WGS AF: 0.130 AC: 454 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.3
DANN	Benign	0.36
PhyloP100		-0.15
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: rs493172; hg19: chr11-128882879;