rs10934491

Positions:

• chr3-119349465-A-C
• chr3-119349465-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020754.4(ARHGAP31):​c.101-15851A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 152,048 control chromosomes in the GnomAD database, including 8,195 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 0.31 (8195 hom., cov: 32)
• Consequence: ARHGAP31 NM_020754.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0630

Genes affected

ARHGAP31 (HGNC:29216): (Rho GTPase activating protein 31) This gene encodes a GTPase-activating protein (GAP). A variety of cellular processes are regulated by Rho GTPases which cycle between an inactive form bound to GDP and an active form bound to GTP. This cycling between inactive and active forms is regulated by guanine nucleotide exchange factors and GAPs. The encoded protein is a GAP shown to regulate two GTPases involved in protein trafficking and cell growth. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP31	NM_020754.4	c.101-15851A>C		intron_variant		ENST00000264245.9	NP_065805.2
ARHGAP31	XM_006713714.4	c.101-15851A>C		intron_variant			XP_006713777.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP31	ENST00000264245.9	c.101-15851A>C		intron_variant		1	NM_020754.4	ENSP00000264245	P1
ARHGAP31	ENST00000482743.1	c.14-15851A>C		intron_variant		4		ENSP00000418429

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46314 AN: 151930 Hom.: 8180 Cov.: 32

Gnomad AFR AF: 0.482

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.305 AC: 46380 AN: 152048 Hom.: 8195 Cov.: 32 AF XY: 0.304 AC XY: 22611 AN XY: 74348

Gnomad4 AFR AF: 0.482

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.287

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.187

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.298

Alfa AF: 0.245 Hom.: 2766

Bravo AF: 0.322

Asia WGS AF: 0.409 AC: 1420 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.0
DANN	Benign	0.68

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: rs10934491; hg19: chr3-119068312;