3-119365267-G-A

Variant names:

• chr3-119365267-G-A
• rs116187120
• NM_020754.4:c.101-49G>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.101-49G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00318 in 1,480,920 control chromosomes in the GnomAD database, including 124 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (61 hom., cov: 33)
  • Exomes 𝑓: 0.0019 (63 hom.)
• Consequence: ARHGAP31 NM_020754.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.137
• Publications: 1 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=-0.83).
• BP6: Variant 3-119365267-G-A is Benign according to our data. Variant chr3-119365267-G-A is described in ClinVar as [Benign]. Clinvar id is 1183029.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP31	NM_020754.4	c.101-49G>A		intron_variant	Intron 1 of 11	ENST00000264245.9	NP_065805.2
ARHGAP31	XM_006713714.4	c.101-49G>A		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.101-49G>A		intron_variant	Intron 1 of 11	1	NM_020754.4	ENSP00000264245.4
ARHGAP31	ENST00000482743.1	c.14-49G>A		intron_variant	Intron 1 of 5	4		ENSP00000418429.1

Frequencies

GnomAD3 genomes AF: 0.0146 AC: 2222 AN: 152128 Hom.: 61 Cov.: 33

Gnomad AFR AF: 0.0503

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00570

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.0139

GnomAD2 exomes AF: 0.00386 AC: 882 AN: 228394 AF XY: 0.00306

Gnomad AFR exome AF: 0.0509

Gnomad AMR exome AF: 0.00288

Gnomad ASJ exome AF: 0.000917

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000386

Gnomad OTH exome AF: 0.00192

GnomAD4 exome AF: 0.00187 AC: 2482 AN: 1328674 Hom.: 63 Cov.: 19 AF XY: 0.00167 AC XY: 1115 AN XY: 667582

African (AFR) AF: 0.0551 AC: 1678 AN: 30432

American (AMR) AF: 0.00282 AC: 124 AN: 44010

Ashkenazi Jewish (ASJ) AF: 0.000907 AC: 23 AN: 25348

East Asian (EAS) AF: 0.00 AC: 0 AN: 38254

South Asian (SAS) AF: 0.000230 AC: 19 AN: 82678

European-Finnish (FIN) AF: 0.0000431 AC: 2 AN: 46386

Middle Eastern (MID) AF: 0.00472 AC: 26 AN: 5508

European-Non Finnish (NFE) AF: 0.000369 AC: 369 AN: 1000100

Other (OTH) AF: 0.00431 AC: 241 AN: 55958

GnomAD4 genome AF: 0.0146 AC: 2223 AN: 152246 Hom.: 61 Cov.: 33 AF XY: 0.0146 AC XY: 1084 AN XY: 74430

African (AFR) AF: 0.0502 AC: 2085 AN: 41526

American (AMR) AF: 0.00569 AC: 87 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68026

Other (OTH) AF: 0.0137 AC: 29 AN: 2110

Alfa AF: 0.00790 Hom.: 8

Bravo AF: 0.0170

Asia WGS AF: 0.00404 AC: 14 AN: 3478

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

- -

Feb 16, 2020

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	-0.83
CADD	Benign	0.70
DANN	Benign	0.53
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism

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: rs116187120; hg19: chr3-119084114;