3-119411294-G-A

Variant names:

• chr3-119411294-G-A
• rs9855065
• NM_020754.4:c.1926+1518G>A

Variant summary

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

The NM_020754.4(ARHGAP31):​c.1926+1518G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,146 control chromosomes in the GnomAD database, including 1,987 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 0.16 (1987 hom., cov: 32)
• Consequence: ARHGAP31 NM_020754.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860
• Publications: 10 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020754.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP31	NM_020754.4	MANE Select	c.1926+1518G>A		intron	N/A	NP_065805.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP31	ENST00000264245.9	TSL:1 MANE Select	c.1926+1518G>A		intron	N/A	ENSP00000264245.4

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23847 AN: 152028 Hom.: 1989 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.157 AC: 23851 AN: 152146 Hom.: 1987 Cov.: 32 AF XY: 0.155 AC XY: 11521 AN XY: 74390

African (AFR) AF: 0.113 AC: 4677 AN: 41492

American (AMR) AF: 0.125 AC: 1915 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 479 AN: 3468

East Asian (EAS) AF: 0.336 AC: 1736 AN: 5166

South Asian (SAS) AF: 0.200 AC: 963 AN: 4820

European-Finnish (FIN) AF: 0.119 AC: 1260 AN: 10606

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.180 AC: 12229 AN: 67986

Other (OTH) AF: 0.160 AC: 338 AN: 2110

Alfa AF: 0.104 Hom.: 190

Bravo AF: 0.155

Asia WGS AF: 0.241 AC: 835 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.4
DANN	Benign	0.65
PhyloP100		-0.086
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: rs9855065; hg19: chr3-119130141;