rs17203055

Positions:

• chr3-119365484-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020754.4(ARHGAP31):​c.203+66A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,394,956 control chromosomes in the GnomAD database, including 9,614 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.098 (981 hom., cov: 32)
  • Exomes 𝑓: 0.11 (8633 hom.)
• Consequence: ARHGAP31 NM_020754.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0770

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 3-119365484-A-G is Benign according to our data. Variant chr3-119365484-A-G is described in ClinVar as [Benign]. Clinvar id is 1273175.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP31	NM_020754.4	c.203+66A>G		intron_variant		ENST00000264245.9
ARHGAP31	XM_006713714.4	c.203+66A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP31	ENST00000264245.9	c.203+66A>G		intron_variant		1	NM_020754.4	P1
ARHGAP31	ENST00000482743.1	c.116+66A>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0983 AC: 14957 AN: 152094 Hom.: 979 Cov.: 32

Gnomad AFR AF: 0.0431

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0881

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.114

GnomAD4 exome AF: 0.109 AC: 136063 AN: 1242744 Hom.: 8633 AF XY: 0.108 AC XY: 67973 AN XY: 627546

Gnomad4 AFR exome AF: 0.0421

Gnomad4 AMR exome AF: 0.272

Gnomad4 ASJ exome AF: 0.126

Gnomad4 EAS exome AF: 0.000428

Gnomad4 SAS exome AF: 0.0958

Gnomad4 FIN exome AF: 0.101

Gnomad4 NFE exome AF: 0.110

Gnomad4 OTH exome AF: 0.110

GnomAD4 genome AF: 0.0984 AC: 14979 AN: 152212 Hom.: 981 Cov.: 32 AF XY: 0.0996 AC XY: 7414 AN XY: 74426

Gnomad4 AFR AF: 0.0433

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0888

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.113

Alfa AF: 0.102 Hom.: 230

Bravo AF: 0.106

Asia WGS AF: 0.0500 AC: 173 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.58
DANN	Benign	0.23

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

Publications

LitVar

Other links and lift over

dbSNP: rs17203055; hg19: chr3-119084331;