rs4687994

Variant names:

• chr3-119294711-G-A
• rs4687994
• NM_020754.4:c.-194G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-119294711-G-A
• chr3-119294711-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020754.4(ARHGAP31):​c.-194G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 625,872 control chromosomes in the GnomAD database, including 47,815 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.35 (9948 hom., cov: 30)
  • Exomes 𝑓: 0.40 (37867 hom.)
• Consequence: ARHGAP31 NM_020754.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.324
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP31	NM_020754.4	c.-194G>A		5_prime_UTR_variant	Exon 1 of 12	ENST00000264245.9	NP_065805.2
ARHGAP31	XM_006713714.4	c.-194G>A		5_prime_UTR_variant	Exon 1 of 12		XP_006713777.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP31	ENST00000264245.9	c.-194G>A		5_prime_UTR_variant	Exon 1 of 12	1	NM_020754.4	ENSP00000264245.4

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53535 AN: 151606 Hom.: 9954 Cov.: 30

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.348

GnomAD4 exome AF: 0.396 AC: 187757 AN: 474148 Hom.: 37867 Cov.: 4 AF XY: 0.396 AC XY: 100122 AN XY: 252770

African (AFR) AF: 0.247 AC: 3175 AN: 12874

American (AMR) AF: 0.300 AC: 6506 AN: 21696

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 6154 AN: 14422

East Asian (EAS) AF: 0.343 AC: 10757 AN: 31380

South Asian (SAS) AF: 0.375 AC: 18611 AN: 49672

European-Finnish (FIN) AF: 0.465 AC: 14005 AN: 30138

Middle Eastern (MID) AF: 0.317 AC: 648 AN: 2044

European-Non Finnish (NFE) AF: 0.413 AC: 117674 AN: 284958

Other (OTH) AF: 0.379 AC: 10227 AN: 26964

GnomAD4 genome AF: 0.353 AC: 53522 AN: 151724 Hom.: 9948 Cov.: 30 AF XY: 0.353 AC XY: 26171 AN XY: 74128

African (AFR) AF: 0.247 AC: 10254 AN: 41436

American (AMR) AF: 0.308 AC: 4706 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 1379 AN: 3466

East Asian (EAS) AF: 0.295 AC: 1505 AN: 5108

South Asian (SAS) AF: 0.371 AC: 1786 AN: 4818

European-Finnish (FIN) AF: 0.447 AC: 4704 AN: 10522

Middle Eastern (MID) AF: 0.336 AC: 98 AN: 292

European-Non Finnish (NFE) AF: 0.414 AC: 28088 AN: 67816

Other (OTH) AF: 0.345 AC: 724 AN: 2100

Alfa AF: 0.365 Hom.: 1847

Bravo AF: 0.336

Asia WGS AF: 0.332 AC: 1157 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	13
DANN	Benign	0.93
PhyloP100		-0.32
PromoterAI		-0.012	Neutral
Mutation Taster		=300/0	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: rs4687994; hg19: chr3-119013558;