3-119294756-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_020754.4(ARHGAP31):c.-149G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0174 in 752,940 control chromosomes in the GnomAD database, including 159 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (32 hom., cov: 31)
  • Exomes 𝑓: 0.018 (127 hom.)
• Consequence: ARHGAP31 NM_020754.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.372

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=-0.79).
• BP6: Variant 3-119294756-G-A is Benign according to our data. Variant chr3-119294756-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1213601.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0143 (2175/152122) while in subpopulation NFE AF= 0.0203 (1379/67964). AF 95% confidence interval is 0.0194. There are 32 homozygotes in gnomad4. There are 1146 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd at 2174 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP31	NM_020754.4	c.-149G>A		5_prime_UTR_variant	1/12	ENST00000264245.9
ARHGAP31	XM_006713714.4	c.-149G>A		5_prime_UTR_variant	1/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP31	ENST00000264245.9	c.-149G>A		5_prime_UTR_variant	1/12	1	NM_020754.4	P1

Frequencies

GnomAD3 genomes AF: 0.0143 AC: 2174 AN: 152004 Hom.: 32 Cov.: 31

Gnomad AFR AF: 0.00408

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.00773

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.0151

Gnomad FIN AF: 0.0332

Gnomad MID AF: 0.0255

Gnomad NFE AF: 0.0203

Gnomad OTH AF: 0.0125

GnomAD4 exome AF: 0.0182 AC: 10931 AN: 600818 Hom.: 127 Cov.: 8 AF XY: 0.0186 AC XY: 5943 AN XY: 320376

Gnomad4 AFR exome AF: 0.00306

Gnomad4 AMR exome AF: 0.00580

Gnomad4 ASJ exome AF: 0.00918

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0178

Gnomad4 FIN exome AF: 0.0329

Gnomad4 NFE exome AF: 0.0208

Gnomad4 OTH exome AF: 0.0152

GnomAD4 genome AF: 0.0143 AC: 2175 AN: 152122 Hom.: 32 Cov.: 31 AF XY: 0.0154 AC XY: 1146 AN XY: 74366

Gnomad4 AFR AF: 0.00407

Gnomad4 AMR AF: 0.00778

Gnomad4 ASJ AF: 0.00893

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.0153

Gnomad4 FIN AF: 0.0332

Gnomad4 NFE AF: 0.0203

Gnomad4 OTH AF: 0.0123

Alfa AF: 0.0201 Hom.: 4

Bravo AF: 0.0113

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 12, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	15
Dann	Benign	0.94

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: rs62265186; hg19: chr3-119013603;