3-119295081-A-T

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.100+77A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 1,375,806 control chromosomes in the GnomAD database, including 153,843 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (16301 hom., cov: 25)
  • Exomes 𝑓: 0.47 (137542 hom.)
• Consequence: ARHGAP31 NM_020754.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.846

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=-0.86).
• BP6: Variant 3-119295081-A-T is Benign according to our data. Variant chr3-119295081-A-T is described in ClinVar as [Benign]. Clinvar id is 1277783.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP31	NM_020754.4	c.100+77A>T		intron_variant		ENST00000264245.9
ARHGAP31	XM_006713714.4	c.100+77A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP31	ENST00000264245.9	c.100+77A>T		intron_variant		1	NM_020754.4	P1

Frequencies

GnomAD3 genomes AF: 0.472 AC: 69627 AN: 147592 Hom.: 16300 Cov.: 25

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.466

GnomAD4 exome AF: 0.472 AC: 579560 AN: 1228152 Hom.: 137542 AF XY: 0.471 AC XY: 293102 AN XY: 621682

Gnomad4 AFR exome AF: 0.453

Gnomad4 AMR exome AF: 0.544

Gnomad4 ASJ exome AF: 0.476

Gnomad4 EAS exome AF: 0.466

Gnomad4 SAS exome AF: 0.474

Gnomad4 FIN exome AF: 0.507

Gnomad4 NFE exome AF: 0.468

Gnomad4 OTH exome AF: 0.457

GnomAD4 genome AF: 0.472 AC: 69654 AN: 147654 Hom.: 16301 Cov.: 25 AF XY: 0.473 AC XY: 33926 AN XY: 71700

Gnomad4 AFR AF: 0.465

Gnomad4 AMR AF: 0.495

Gnomad4 ASJ AF: 0.448

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.468

Gnomad4 FIN AF: 0.511

Gnomad4 NFE AF: 0.470

Gnomad4 OTH AF: 0.463

Alfa AF: 0.473 Hom.: 2085

Bravo AF: 0.466

Asia WGS AF: 0.448 AC: 1562 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

Oct 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	5.5
Dann	Benign	0.60

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: rs3732412; hg19: chr3-119013928; COSMIC: COSV51788867; COSMIC: COSV51788867;