chr3-119312113-A-G

Variant names:

• chr3-119312113-A-G
• rs10934490
• NM_020754.4:c.100+17109A>G

Variant summary

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

The NM_020754.4(ARHGAP31):​c.100+17109A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 152,120 control chromosomes in the GnomAD database, including 11,575 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 0.39 (11575 hom., cov: 33)
• Consequence: ARHGAP31 NM_020754.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP31	NM_020754.4	c.100+17109A>G		intron_variant	Intron 1 of 11	ENST00000264245.9	NP_065805.2
ARHGAP31	XM_006713714.4	c.100+17109A>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.100+17109A>G		intron_variant	Intron 1 of 11	1	NM_020754.4	ENSP00000264245.4

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58808 AN: 152000 Hom.: 11577 Cov.: 33

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.386

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

GnomAD4 genome AF: 0.387 AC: 58821 AN: 152120 Hom.: 11575 Cov.: 33 AF XY: 0.387 AC XY: 28749 AN XY: 74364

African (AFR) AF: 0.363 AC: 15042 AN: 41480

American (AMR) AF: 0.307 AC: 4692 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.412 AC: 1430 AN: 3470

East Asian (EAS) AF: 0.366 AC: 1898 AN: 5188

South Asian (SAS) AF: 0.399 AC: 1923 AN: 4822

European-Finnish (FIN) AF: 0.447 AC: 4726 AN: 10570

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.412 AC: 27974 AN: 67976

Other (OTH) AF: 0.382 AC: 807 AN: 2114

Alfa AF: 0.409 Hom.: 1646

Bravo AF: 0.373

Asia WGS AF: 0.355 AC: 1239 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.38
DANN	Benign	0.40
PhyloP100		-1.5
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: rs10934490; hg19: chr3-119030960;