3-119409781-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020754.4(ARHGAP31):c.1926+5A>G variant causes a splice donor 5th base, 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_donor_5th_base, intron

Scores

Splicing: ADA: 0.00005967

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.36

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	UniProt
ARHGAP31	NM_020754.4 linkuse as main transcript	c.1926+5A>G		splice_donor_5th_base_variant, intron_variant		ENST00000264245.9
ARHGAP31	XM_006713714.4 linkuse as main transcript	c.1866+5A>G		splice_donor_5th_base_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP31	ENST00000264245.9 linkuse as main transcript	c.1926+5A>G		splice_donor_5th_base_variant, intron_variant		1	NM_020754.4	P1

Frequencies

GnomAD3 genomes

AF:

0.652

AC:

99063

AN:

151864

Hom.:

32554

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.624

AC XY:

446682

AN XY:

715750

show subpopulations

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.:

AF XY:

0.656

AC XY:

48730

AN XY:

74254

show subpopulations

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:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over