rs2155177

Positions:

• chr11-129041538-A-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.83).
• 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	UniProt
ARHGAP32	NM_001378024.1	c.964-529T>G		intron_variant		ENST00000682385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP32	ENST00000682385.1	c.964-529T>G		intron_variant			NM_001378024.1	P3
ARHGAP32	ENST00000310343.13	c.922-529T>G		intron_variant		1		A1
ARHGAP32	ENST00000524655.5	c.700-529T>G		intron_variant		1
ARHGAP32	ENST00000533509.1	n.378-529T>G		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.372

Gnomad4 EAS AF: 0.307

Gnomad4 SAS AF: 0.168

Gnomad4 FIN AF: 0.210

Gnomad4 NFE AF: 0.323

Gnomad4 OTH AF: 0.324

Alfa AF: 0.298 Hom.: 3176

Bravo AF: 0.288

Asia WGS AF: 0.213 AC: 739 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.0
DANN	Benign	0.33

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

Publications

LitVar

Other links and lift over

dbSNP: rs2155177; hg19: chr11-128911433;