rs1060503817

chr17-8313079-T-Achr17-8313079-T-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_173728.4(ARHGEF15):c.759T>A(p.Pro253=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P253P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000060 (0 hom., cov: 26)
  • Exomes 𝑓: 0.0016 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARHGEF15 NM_173728.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900

Genes affected

ARHGEF15 (HGNC:15590): (Rho guanine nucleotide exchange factor 15) Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli that work through G protein-coupled receptors. This gene encodes a protein that functions as a specific guanine nucleotide exchange factor for RhoA. It also interacts with ephrin A4 in vascular smooth muscle cells. Two alternatively spliced transcripts variants that encode the same protein have been found for this gene. [provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP7: Synonymous conserved (PhyloP=-0.009 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF15	NM_173728.4	c.759T>A	p.Pro253=	synonymous_variant	3/16	ENST00000361926.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF15	ENST00000361926.8	c.759T>A	p.Pro253=	synonymous_variant	3/16	1	NM_173728.4	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 5 AN: 83440 Hom.: 0 Cov.: 26 FAILED QC

Gnomad AFR AF: 0.0000453

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000424

Gnomad FIN AF: 0.000220

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000503

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00156 AC: 1304 AN: 834222 Hom.: 0 Cov.: 34 AF XY: 0.00149 AC XY: 633 AN XY: 423668

Gnomad4 AFR exome AF: 0.00111

Gnomad4 AMR exome AF: 0.0000868

Gnomad4 ASJ exome AF: 0.000658

Gnomad4 EAS exome AF: 0.0000767

Gnomad4 SAS exome AF: 0.000418

Gnomad4 FIN exome AF: 0.000272

Gnomad4 NFE exome AF: 0.00197

Gnomad4 OTH exome AF: 0.00134

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000599 AC: 5 AN: 83474 Hom.: 0 Cov.: 26 AF XY: 0.000100 AC XY: 4 AN XY: 39952

Gnomad4 AFR AF: 0.0000453

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000424

Gnomad4 FIN AF: 0.000220

Gnomad4 NFE AF: 0.0000503

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	6.5
Dann	Benign	0.60

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-8216397;