3-119294711-G-A

Position:

• chr3-119294711-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.-194G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 625,872 control chromosomes in the GnomAD database, including 47,815 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (9948 hom., cov: 30)
  • Exomes 𝑓: 0.40 (37867 hom.)
• Consequence: ARHGAP31 NM_020754.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.324

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=-0.88).
• BP6: Variant 3-119294711-G-A is Benign according to our data. Variant chr3-119294711-G-A is described in ClinVar as [Benign]. Clinvar id is 1287086.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP31	NM_020754.4	c.-194G>A		5_prime_UTR_variant	1/12	ENST00000264245.9	NP_065805.2
ARHGAP31	XM_006713714.4	c.-194G>A		5_prime_UTR_variant	1/12		XP_006713777.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP31	ENST00000264245	c.-194G>A		5_prime_UTR_variant	1/12	1	NM_020754.4	ENSP00000264245.4

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53535 AN: 151606 Hom.: 9954 Cov.: 30

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.348

GnomAD4 exome AF: 0.396 AC: 187757 AN: 474148 Hom.: 37867 Cov.: 4 AF XY: 0.396 AC XY: 100122 AN XY: 252770

Gnomad4 AFR exome AF: 0.247

Gnomad4 AMR exome AF: 0.300

Gnomad4 ASJ exome AF: 0.427

Gnomad4 EAS exome AF: 0.343

Gnomad4 SAS exome AF: 0.375

Gnomad4 FIN exome AF: 0.465

Gnomad4 NFE exome AF: 0.413

Gnomad4 OTH exome AF: 0.379

GnomAD4 genome AF: 0.353 AC: 53522 AN: 151724 Hom.: 9948 Cov.: 30 AF XY: 0.353 AC XY: 26171 AN XY: 74128

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.308

Gnomad4 ASJ AF: 0.398

Gnomad4 EAS AF: 0.295

Gnomad4 SAS AF: 0.371

Gnomad4 FIN AF: 0.447

Gnomad4 NFE AF: 0.414

Gnomad4 OTH AF: 0.345

Alfa AF: 0.365 Hom.: 1847

Bravo AF: 0.336

Asia WGS AF: 0.332 AC: 1157 AN: 3476

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.88
CADD	Benign	13
DANN	Benign	0.93

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: rs4687994; hg19: chr3-119013558;