3-119365279-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020754.4(ARHGAP31):c.101-37C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.022 in 1,549,688 control chromosomes in the GnomAD database, including 557 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (47 hom., cov: 33)
  • Exomes 𝑓: 0.023 (510 hom.)
• Consequence: ARHGAP31 NM_020754.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0260

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 3-119365279-C-A is Benign according to our data. Variant chr3-119365279-C-A is described in ClinVar as [Benign]. Clinvar id is 1250667.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP31	NM_020754.4	c.101-37C>A		intron_variant		ENST00000264245.9
ARHGAP31	XM_006713714.4	c.101-37C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP31	ENST00000264245.9	c.101-37C>A		intron_variant		1	NM_020754.4	P1
ARHGAP31	ENST00000482743.1	c.14-37C>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0172 AC: 2622 AN: 152110 Hom.: 47 Cov.: 33

Gnomad AFR AF: 0.00328

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00511

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.0610

Gnomad SAS AF: 0.0425

Gnomad FIN AF: 0.0484

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.0191

Gnomad OTH AF: 0.0158

GnomAD3 exomes AF: 0.0236 AC: 5646 AN: 238784 Hom.: 114 AF XY: 0.0253 AC XY: 3291 AN XY: 130192

Gnomad AFR exome AF: 0.00249

Gnomad AMR exome AF: 0.00436

Gnomad ASJ exome AF: 0.0107

Gnomad EAS exome AF: 0.0624

Gnomad SAS exome AF: 0.0394

Gnomad FIN exome AF: 0.0441

Gnomad NFE exome AF: 0.0198

Gnomad OTH exome AF: 0.0260

GnomAD4 exome AF: 0.0226 AC: 31517 AN: 1397460 Hom.: 510 Cov.: 23 AF XY: 0.0233 AC XY: 16269 AN XY: 698788

Gnomad4 AFR exome AF: 0.00375

Gnomad4 AMR exome AF: 0.00449

Gnomad4 ASJ exome AF: 0.0112

Gnomad4 EAS exome AF: 0.0753

Gnomad4 SAS exome AF: 0.0379

Gnomad4 FIN exome AF: 0.0463

Gnomad4 NFE exome AF: 0.0200

Gnomad4 OTH exome AF: 0.0218

GnomAD4 genome AF: 0.0172 AC: 2622 AN: 152228 Hom.: 47 Cov.: 33 AF XY: 0.0184 AC XY: 1369 AN XY: 74424

Gnomad4 AFR AF: 0.00327

Gnomad4 AMR AF: 0.00510

Gnomad4 ASJ AF: 0.0104

Gnomad4 EAS AF: 0.0607

Gnomad4 SAS AF: 0.0427

Gnomad4 FIN AF: 0.0484

Gnomad4 NFE AF: 0.0191

Gnomad4 OTH AF: 0.0161

Alfa AF: 0.0107 Hom.: 0

Bravo AF: 0.0134

Asia WGS AF: 0.0490 AC: 172 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
Cadd	Benign	7.5
Dann	Benign	0.53

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: rs113568026; hg19: chr3-119084126;