3-119294867-C-A

Variant names:

• chr3-119294867-C-A
• rs72960626
• NM_020754.4:c.-38C>A

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.-38C>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 0.0639 in 1,583,690 control chromosomes in the GnomAD database, including 4,509 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.084 (708 hom., cov: 31)
  • Exomes 𝑓: 0.062 (3801 hom.)
• Consequence: ARHGAP31 NM_020754.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0480
• 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=-0.61).
• BP6: Variant 3-119294867-C-A is Benign according to our data. Variant chr3-119294867-C-A is described in ClinVar as [Benign]. Clinvar id is 342625.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP31	NM_020754.4	c.-38C>A		5_prime_UTR_variant	Exon 1 of 12	ENST00000264245.9	NP_065805.2
ARHGAP31	XM_006713714.4	c.-38C>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.-38C>A		5_prime_UTR_variant	Exon 1 of 12	1	NM_020754.4	ENSP00000264245.4

Frequencies

GnomAD3 genomes AF: 0.0836 AC: 12694 AN: 151828 Hom.: 709 Cov.: 31

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.0793

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.0473

Gnomad EAS AF: 0.0740

Gnomad SAS AF: 0.0881

Gnomad FIN AF: 0.0381

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0525

Gnomad OTH AF: 0.0866

GnomAD2 exomes AF: 0.0887 AC: 22082 AN: 248946 AF XY: 0.0817

Gnomad AFR exome AF: 0.122

Gnomad AMR exome AF: 0.250

Gnomad ASJ exome AF: 0.0485

Gnomad EAS exome AF: 0.0713

Gnomad FIN exome AF: 0.0363

Gnomad NFE exome AF: 0.0508

Gnomad OTH exome AF: 0.0769

GnomAD4 exome AF: 0.0618 AC: 88468 AN: 1431744 Hom.: 3801 Cov.: 27 AF XY: 0.0615 AC XY: 43909 AN XY: 714196

African (AFR) AF: 0.121 AC: 3991 AN: 32870

American (AMR) AF: 0.242 AC: 10786 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.0478 AC: 1239 AN: 25942

East Asian (EAS) AF: 0.0546 AC: 2160 AN: 39588

South Asian (SAS) AF: 0.0951 AC: 8146 AN: 85628

European-Finnish (FIN) AF: 0.0381 AC: 2030 AN: 53250

Middle Eastern (MID) AF: 0.0692 AC: 366 AN: 5288

European-Non Finnish (NFE) AF: 0.0515 AC: 55840 AN: 1085116

Other (OTH) AF: 0.0658 AC: 3910 AN: 59400

GnomAD4 genome AF: 0.0837 AC: 12716 AN: 151946 Hom.: 708 Cov.: 31 AF XY: 0.0838 AC XY: 6226 AN XY: 74256

African (AFR) AF: 0.119 AC: 4927 AN: 41458

American (AMR) AF: 0.168 AC: 2575 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0473 AC: 164 AN: 3468

East Asian (EAS) AF: 0.0742 AC: 379 AN: 5110

South Asian (SAS) AF: 0.0890 AC: 429 AN: 4818

European-Finnish (FIN) AF: 0.0381 AC: 402 AN: 10556

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0525 AC: 3564 AN: 67940

Other (OTH) AF: 0.0857 AC: 181 AN: 2112

Alfa AF: 0.0634 Hom.: 585

Bravo AF: 0.0982

Asia WGS AF: 0.0840 AC: 292 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

- -

Nov 08, 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	-0.61
CADD	Benign	16
DANN	Benign	0.71
PhyloP100		0.048
PromoterAI		0.019	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: rs72960626; hg19: chr3-119013714; COSMIC: COSV51790779; COSMIC: COSV51790779;