3-119365022-A-G

Variant names:

• chr3-119365022-A-G
• rs143737497
• NM_020754.4:c.101-294A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020754.4(ARHGAP31):​c.101-294A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0172 in 152,250 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.017 (47 hom., cov: 33)
• Consequence: ARHGAP31 NM_020754.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.682
• Publications: 0 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 3-119365022-A-G is Benign according to our data. Variant chr3-119365022-A-G is described in ClinVar as [Benign]. Clinvar id is 1259498.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP31	NM_020754.4	c.101-294A>G		intron_variant	Intron 1 of 11	ENST00000264245.9	NP_065805.2
ARHGAP31	XM_006713714.4	c.101-294A>G		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.101-294A>G		intron_variant	Intron 1 of 11	1	NM_020754.4	ENSP00000264245.4
ARHGAP31	ENST00000482743.1	c.14-294A>G		intron_variant	Intron 1 of 5	4		ENSP00000418429.1

Frequencies

GnomAD3 genomes AF: 0.0172 AC: 2621 AN: 152132 Hom.: 47 Cov.: 33

Gnomad AFR AF: 0.00331

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00511

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.0608

Gnomad SAS AF: 0.0420

Gnomad FIN AF: 0.0484

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0192

Gnomad OTH AF: 0.0158

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0172 AC: 2621 AN: 152250 Hom.: 47 Cov.: 33 AF XY: 0.0184 AC XY: 1369 AN XY: 74440

African (AFR) AF: 0.00330 AC: 137 AN: 41554

American (AMR) AF: 0.00510 AC: 78 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0104 AC: 36 AN: 3472

East Asian (EAS) AF: 0.0606 AC: 313 AN: 5166

South Asian (SAS) AF: 0.0423 AC: 204 AN: 4828

European-Finnish (FIN) AF: 0.0484 AC: 513 AN: 10604

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

European-Non Finnish (NFE) AF: 0.0192 AC: 1304 AN: 68010

Other (OTH) AF: 0.0161 AC: 34 AN: 2114

Alfa AF: 0.0193 Hom.: 2

Bravo AF: 0.0134

Asia WGS AF: 0.0490 AC: 172 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.90
CADD	Benign	4.4
DANN	Benign	0.79
PhyloP100		0.68
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: rs143737497; hg19: chr3-119083869;