rs6766899

Variant names:

• chr3-119388405-T-G
• rs6766899
• NM_020754.4:c.683-2380T>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.683-2380T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.814 in 151,048 control chromosomes in the GnomAD database, including 50,254 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 0.81 (50254 hom., cov: 28)
• Consequence: ARHGAP31 NM_020754.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190
• Publications: 8 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.894 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.683-2380T>G		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.683-2380T>G		intron	N/A	ENSP00000264245.4

Frequencies

GnomAD3 genomes AF: 0.814 AC: 122797 AN: 150938 Hom.: 50209 Cov.: 28

Gnomad AFR AF: 0.901

Gnomad AMI AF: 0.790

Gnomad AMR AF: 0.739

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.908

Gnomad SAS AF: 0.860

Gnomad FIN AF: 0.752

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.779

Gnomad OTH AF: 0.806

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

GnomAD4 genome AF: 0.814 AC: 122894 AN: 151048 Hom.: 50254 Cov.: 28 AF XY: 0.811 AC XY: 59826 AN XY: 73780

African (AFR) AF: 0.901 AC: 37098 AN: 41152

American (AMR) AF: 0.739 AC: 11225 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.762 AC: 2637 AN: 3462

East Asian (EAS) AF: 0.908 AC: 4613 AN: 5078

South Asian (SAS) AF: 0.858 AC: 4100 AN: 4776

European-Finnish (FIN) AF: 0.752 AC: 7733 AN: 10282

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.779 AC: 52851 AN: 67814

Other (OTH) AF: 0.806 AC: 1685 AN: 2090

Alfa AF: 0.795 Hom.: 93352

Bravo AF: 0.815

Asia WGS AF: 0.878 AC: 3052 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.9
DANN	Benign	0.72
PhyloP100		0.019
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: rs6766899; hg19: chr3-119107252;