3-119294867-C-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.-38C>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 0.0639 in 1,583,690 control chromosomes in the GnomAD database, including 4,509 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.084 (708 hom., cov: 31)
  • Exomes 𝑓: 0.062 (3801 hom.)
• Consequence: ARHGAP31 NM_020754.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0480

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=-0.61).
• BP6: Variant 3-119294867-C-A is Benign according to our data. Variant chr3-119294867-C-A is described in ClinVar as [Benign]. Clinvar id is 342625.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP31	NM_020754.4	c.-38C>A		5_prime_UTR_variant	1/12	ENST00000264245.9
ARHGAP31	XM_006713714.4	c.-38C>A		5_prime_UTR_variant	1/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP31	ENST00000264245.9	c.-38C>A		5_prime_UTR_variant	1/12	1	NM_020754.4	P1

Frequencies

GnomAD3 genomes AF: 0.0836 AC: 12694 AN: 151828 Hom.: 709 Cov.: 31

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.0793

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.0473

Gnomad EAS AF: 0.0740

Gnomad SAS AF: 0.0881

Gnomad FIN AF: 0.0381

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0525

Gnomad OTH AF: 0.0866

GnomAD3 exomes AF: 0.0887 AC: 22082 AN: 248946 Hom.: 1693 AF XY: 0.0817 AC XY: 11042 AN XY: 135168

Gnomad AFR exome AF: 0.122

Gnomad AMR exome AF: 0.250

Gnomad ASJ exome AF: 0.0485

Gnomad EAS exome AF: 0.0713

Gnomad SAS exome AF: 0.0924

Gnomad FIN exome AF: 0.0363

Gnomad NFE exome AF: 0.0508

Gnomad OTH exome AF: 0.0769

GnomAD4 exome AF: 0.0618 AC: 88468 AN: 1431744 Hom.: 3801 Cov.: 27 AF XY: 0.0615 AC XY: 43909 AN XY: 714196

Gnomad4 AFR exome AF: 0.121

Gnomad4 AMR exome AF: 0.242

Gnomad4 ASJ exome AF: 0.0478

Gnomad4 EAS exome AF: 0.0546

Gnomad4 SAS exome AF: 0.0951

Gnomad4 FIN exome AF: 0.0381

Gnomad4 NFE exome AF: 0.0515

Gnomad4 OTH exome AF: 0.0658

GnomAD4 genome AF: 0.0837 AC: 12716 AN: 151946 Hom.: 708 Cov.: 31 AF XY: 0.0838 AC XY: 6226 AN XY: 74256

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.0473

Gnomad4 EAS AF: 0.0742

Gnomad4 SAS AF: 0.0890

Gnomad4 FIN AF: 0.0381

Gnomad4 NFE AF: 0.0525

Gnomad4 OTH AF: 0.0857

Alfa AF: 0.0643 Hom.: 122

Bravo AF: 0.0982

Asia WGS AF: 0.0840 AC: 292 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Adams-Oliver syndrome 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
Cadd	Benign	16
Dann	Benign	0.71

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: rs72960626; hg19: chr3-119013714; COSMIC: COSV51790779; COSMIC: COSV51790779;