NM_020754.4:c.101-330C>T

Variant names:

• chr3-119364986-C-T
• rs6438524
• NM_020754.4:c.101-330C>T

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.101-330C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 151,794 control chromosomes in the GnomAD database, including 14,910 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.41 (14910 hom., cov: 31)
• Consequence: ARHGAP31 NM_020754.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.842
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BP6: Variant 3-119364986-C-T is Benign according to our data. Variant chr3-119364986-C-T is described in ClinVar as [Benign]. Clinvar id is 1255081.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP31	NM_020754.4	c.101-330C>T		intron_variant	Intron 1 of 11	ENST00000264245.9	NP_065805.2
ARHGAP31	XM_006713714.4	c.101-330C>T		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.101-330C>T		intron_variant	Intron 1 of 11	1	NM_020754.4	ENSP00000264245.4
ARHGAP31	ENST00000482743.1	c.14-330C>T		intron_variant	Intron 1 of 5	4		ENSP00000418429.1

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62489 AN: 151676 Hom.: 14876 Cov.: 31

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.391

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

GnomAD4 genome AF: 0.412 AC: 62587 AN: 151794 Hom.: 14910 Cov.: 31 AF XY: 0.410 AC XY: 30443 AN XY: 74174

African (AFR) AF: 0.668 AC: 27643 AN: 41390

American (AMR) AF: 0.386 AC: 5888 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 984 AN: 3468

East Asian (EAS) AF: 0.325 AC: 1673 AN: 5146

South Asian (SAS) AF: 0.506 AC: 2425 AN: 4794

European-Finnish (FIN) AF: 0.269 AC: 2837 AN: 10528

Middle Eastern (MID) AF: 0.356 AC: 104 AN: 292

European-Non Finnish (NFE) AF: 0.292 AC: 19855 AN: 67922

Other (OTH) AF: 0.393 AC: 827 AN: 2102

Alfa AF: 0.373 Hom.: 1597

Bravo AF: 0.432

Asia WGS AF: 0.456 AC: 1583 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	-1.0
CADD	Benign	1.4
DANN	Benign	0.52
PhyloP100		-0.84
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: rs6438524; hg19: chr3-119083833;