chr11-129041538-A-C

Variant names:

• chr11-129041538-A-C
• rs2155177
• NM_001378024.1:c.964-529T>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.964-529T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 151,448 control chromosomes in the GnomAD database, including 6,246 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 (6246 hom., cov: 31)
• Consequence: ARHGAP32 NM_001378024.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.474
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.345 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.964-529T>G		intron	N/A	NP_001364953.1
	ARHGAP32	NM_001142685.2		c.922-529T>G		intron	N/A	NP_001136157.1
	ARHGAP32	NM_001378025.1		c.802-529T>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.964-529T>G		intron	N/A	ENSP00000507720.1
	ARHGAP32	ENST00000310343.13	TSL:1	c.922-529T>G		intron	N/A	ENSP00000310561.8
	ARHGAP32	ENST00000524655.5	TSL:1	c.700-529T>G		intron	N/A	ENSP00000432468.1

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41677 AN: 151336 Hom.: 6245 Cov.: 31

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.275 AC: 41687 AN: 151448 Hom.: 6246 Cov.: 31 AF XY: 0.269 AC XY: 19931 AN XY: 73998

African (AFR) AF: 0.181 AC: 7491 AN: 41344

American (AMR) AF: 0.352 AC: 5366 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1288 AN: 3464

East Asian (EAS) AF: 0.307 AC: 1581 AN: 5144

South Asian (SAS) AF: 0.168 AC: 808 AN: 4812

European-Finnish (FIN) AF: 0.210 AC: 2157 AN: 10278

Middle Eastern (MID) AF: 0.411 AC: 120 AN: 292

European-Non Finnish (NFE) AF: 0.323 AC: 21941 AN: 67882

Other (OTH) AF: 0.324 AC: 681 AN: 2104

Alfa AF: 0.301 Hom.: 3623

Bravo AF: 0.288

Asia WGS AF: 0.213 AC: 739 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.0
DANN	Benign	0.33
PhyloP100		0.47
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: rs2155177; hg19: chr11-128911433;