3-119409781-A-G

Variant names:

• chr3-119409781-A-G
• rs1463139
• NM_020754.4:c.1926+5A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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]

ARHGAP31 Gene-Disease associations (from GenCC):

• Adams-Oliver syndrome 1

  Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• Adams-Oliver syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 342651.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020754.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP31	NM_020754.4	MANE Select	c.1926+5A>G		splice_region intron	N/A	NP_065805.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP31	ENST00000264245.9	TSL:1 MANE Select	c.1926+5A>G		splice_region intron	N/A	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

GnomAD2 exomes AF: 0.623 AC: 134880 AN: 216484 AF XY: 0.624

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 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

African (AFR) AF: 0.727 AC: 24041 AN: 33054

American (AMR) AF: 0.616 AC: 26017 AN: 42256

Ashkenazi Jewish (ASJ) AF: 0.574 AC: 14773 AN: 25734

East Asian (EAS) AF: 0.563 AC: 21950 AN: 39018

South Asian (SAS) AF: 0.673 AC: 56250 AN: 83590

European-Finnish (FIN) AF: 0.714 AC: 37175 AN: 52088

Middle Eastern (MID) AF: 0.600 AC: 2547 AN: 4248

European-Non Finnish (NFE) AF: 0.616 AC: 679011 AN: 1102514

Other (OTH) AF: 0.617 AC: 36723 AN: 59492

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

African (AFR) AF: 0.720 AC: 29878 AN: 41472

American (AMR) AF: 0.647 AC: 9886 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 2019 AN: 3472

East Asian (EAS) AF: 0.526 AC: 2713 AN: 5160

South Asian (SAS) AF: 0.667 AC: 3215 AN: 4822

European-Finnish (FIN) AF: 0.728 AC: 7662 AN: 10526

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.614 AC: 41697 AN: 67938

Other (OTH) AF: 0.639 AC: 1345 AN: 2104

Alfa AF: 0.627 Hom.: 17602

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Oct 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	17
DANN	Benign	0.86
PhyloP100		1.4
Mutation Taster		=14/86	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1463139; hg19: chr3-119128628; COSMIC: COSV51798601;