3-119295081-A-T

Variant names:

• chr3-119295081-A-T
• rs3732412
• NM_020754.4:c.100+77A>T

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.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:3
• Conservation: PhyloP100: -0.846
• Publications: 5 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=-0.86).
• 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 rank	MANE	Protein	UniProt
ARHGAP31	NM_020754.4	c.100+77A>T		intron_variant	Intron 1 of 11	ENST00000264245.9	NP_065805.2
ARHGAP31	XM_006713714.4	c.100+77A>T		intron_variant	Intron 1 of 11		XP_006713777.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP31	ENST00000264245.9	c.100+77A>T		intron_variant	Intron 1 of 11	1	NM_020754.4	ENSP00000264245.4

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

African (AFR) AF: 0.453 AC: 12980 AN: 28666

American (AMR) AF: 0.544 AC: 23186 AN: 42614

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 11692 AN: 24552

East Asian (EAS) AF: 0.466 AC: 17930 AN: 38450

South Asian (SAS) AF: 0.474 AC: 38304 AN: 80726

European-Finnish (FIN) AF: 0.507 AC: 26565 AN: 52380

Middle Eastern (MID) AF: 0.395 AC: 2089 AN: 5290

European-Non Finnish (NFE) AF: 0.468 AC: 422779 AN: 902844

Other (OTH) AF: 0.457 AC: 24035 AN: 52630

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

African (AFR) AF: 0.465 AC: 18448 AN: 39684

American (AMR) AF: 0.495 AC: 7335 AN: 14822

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1545 AN: 3448

East Asian (EAS) AF: 0.451 AC: 2258 AN: 5012

South Asian (SAS) AF: 0.468 AC: 2163 AN: 4622

European-Finnish (FIN) AF: 0.511 AC: 4938 AN: 9656

Middle Eastern (MID) AF: 0.444 AC: 126 AN: 284

European-Non Finnish (NFE) AF: 0.470 AC: 31555 AN: 67208

Other (OTH) AF: 0.463 AC: 935 AN: 2020

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Adams-Oliver syndrome 1 Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.5
DANN	Benign	0.60
PhyloP100		-0.85
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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