3-119365267-G-A

Position:

• chr3-119365267-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_020754.4(ARHGAP31):​c.101-49G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00318 in 1,480,920 control chromosomes in the GnomAD database, including 124 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (61 hom., cov: 33)
  • Exomes 𝑓: 0.0019 (63 hom.)
• Consequence: ARHGAP31 NM_020754.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.137

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 3-119365267-G-A is Benign according to our data. Variant chr3-119365267-G-A is described in ClinVar as [Benign]. Clinvar id is 1183029.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP31	NM_020754.4	c.101-49G>A		intron_variant		ENST00000264245.9	NP_065805.2
ARHGAP31	XM_006713714.4	c.101-49G>A		intron_variant			XP_006713777.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP31	ENST00000264245.9	c.101-49G>A		intron_variant		1	NM_020754.4	ENSP00000264245.4
ARHGAP31	ENST00000482743.1	c.14-49G>A		intron_variant		4		ENSP00000418429.1

Frequencies

GnomAD3 genomes AF: 0.0146 AC: 2222 AN: 152128 Hom.: 61 Cov.: 33

Gnomad AFR AF: 0.0503

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00570

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.0139

GnomAD3 exomes AF: 0.00386 AC: 882 AN: 228394 Hom.: 25 AF XY: 0.00306 AC XY: 382 AN XY: 124698

Gnomad AFR exome AF: 0.0509

Gnomad AMR exome AF: 0.00288

Gnomad ASJ exome AF: 0.000917

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000240

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000386

Gnomad OTH exome AF: 0.00192

GnomAD4 exome AF: 0.00187 AC: 2482 AN: 1328674 Hom.: 63 Cov.: 19 AF XY: 0.00167 AC XY: 1115 AN XY: 667582

Gnomad4 AFR exome AF: 0.0551

Gnomad4 AMR exome AF: 0.00282

Gnomad4 ASJ exome AF: 0.000907

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000230

Gnomad4 FIN exome AF: 0.0000431

Gnomad4 NFE exome AF: 0.000369

Gnomad4 OTH exome AF: 0.00431

GnomAD4 genome AF: 0.0146 AC: 2223 AN: 152246 Hom.: 61 Cov.: 33 AF XY: 0.0146 AC XY: 1084 AN XY: 74430

Gnomad4 AFR AF: 0.0502

Gnomad4 AMR AF: 0.00569

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.00856 Hom.: 5

Bravo AF: 0.0170

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 16, 2020	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.70
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: rs116187120; hg19: chr3-119084114;