3-119409781-A-G

Position:

• chr3-119409781-A-G

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.1926+5A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 151,982 control chromosomes in the GnomAD database, including 32,580 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.65 (32580 hom., cov: 33)
  • Exomes 𝑓: 0.62 (281021 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARHGAP31 NM_020754.4 splice_region, intron
• Scores: Splicing: ADA: 0.00005967
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.36

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=-0.6).
• BP6: Variant 3-119409781-A-G is Benign according to our data. Variant chr3-119409781-A-G is described in ClinVar as [Benign]. Clinvar id is 342651.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-119409781-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP31	NM_020754.4	c.1926+5A>G		splice_region_variant, intron_variant		ENST00000264245.9	NP_065805.2
ARHGAP31	XM_006713714.4	c.1866+5A>G		splice_region_variant, intron_variant			XP_006713777.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP31	ENST00000264245.9	c.1926+5A>G		splice_region_variant, intron_variant		1	NM_020754.4	ENSP00000264245.4

Frequencies

GnomAD3 genomes AF: 0.652 AC: 99063 AN: 151864 Hom.: 32554 Cov.: 33

Gnomad AFR AF: 0.721

Gnomad AMI AF: 0.602

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.641

GnomAD3 exomes AF: 0.623 AC: 134880 AN: 216484 Hom.: 42025 AF XY: 0.624 AC XY: 73442 AN XY: 117714

Gnomad AFR exome AF: 0.721

Gnomad AMR exome AF: 0.611

Gnomad ASJ exome AF: 0.566

Gnomad EAS exome AF: 0.525

Gnomad SAS exome AF: 0.671

Gnomad FIN exome AF: 0.717

Gnomad NFE exome AF: 0.604

Gnomad OTH exome AF: 0.616

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.623 AC: 898487 AN: 1441994 Hom.: 281021 Cov.: 46 AF XY: 0.624 AC XY: 446682 AN XY: 715750

Gnomad4 AFR exome AF: 0.727

Gnomad4 AMR exome AF: 0.616

Gnomad4 ASJ exome AF: 0.574

Gnomad4 EAS exome AF: 0.563

Gnomad4 SAS exome AF: 0.673

Gnomad4 FIN exome AF: 0.714

Gnomad4 NFE exome AF: 0.616

Gnomad4 OTH exome AF: 0.617

GnomAD4 genome AF: 0.652 AC: 99142 AN: 151982 Hom.: 32580 Cov.: 33 AF XY: 0.656 AC XY: 48730 AN XY: 74254

Gnomad4 AFR AF: 0.720

Gnomad4 AMR AF: 0.647

Gnomad4 ASJ AF: 0.582

Gnomad4 EAS AF: 0.526

Gnomad4 SAS AF: 0.667

Gnomad4 FIN AF: 0.728

Gnomad4 NFE AF: 0.614

Gnomad4 OTH AF: 0.639

Alfa AF: 0.624 Hom.: 16408

Bravo AF: 0.648

Asia WGS AF: 0.608 AC: 2114 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 16, 2018	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: 64% of total chromosomes in ExAC -

Adams-Oliver syndrome 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	17
DANN	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000060
dbscSNV1_RF	Benign	0.016
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: rs1463139; hg19: chr3-119128628; COSMIC: COSV51798601;