17-8312078-G-C

Position:

• chr17-8312078-G-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.39G>C​(p.Thr13Thr) 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.

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 17)
  • Exomes 𝑓: 0.00015 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARHGEF15 NM_173728.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180

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]

ARHGEF15 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP7: Synonymous conserved (PhyloP=-0.018 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF15	NM_173728.4	c.39G>C	p.Thr13Thr	synonymous_variant	2/16	ENST00000361926.8	NP_776089.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF15	ENST00000361926.8	c.39G>C	p.Thr13Thr	synonymous_variant	2/16	1	NM_173728.4	ENSP00000355026.3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 11 AN: 80600 Hom.: 0 Cov.: 17 FAILED QC

Gnomad AFR AF: 0.000104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000276

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000308

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000153

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000231 AC: 34 AN: 146956 Hom.: 0 AF XY: 0.000223 AC XY: 18 AN XY: 80688

Gnomad AFR exome AF: 0.000288

Gnomad AMR exome AF: 0.000215

Gnomad ASJ exome AF: 0.000246

Gnomad EAS exome AF: 0.000120

Gnomad SAS exome AF: 0.000329

Gnomad FIN exome AF: 0.000347

Gnomad NFE exome AF: 0.000187

Gnomad OTH exome AF: 0.000371

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000151 AC: 188 AN: 1242552 Hom.: 0 Cov.: 35 AF XY: 0.000186 AC XY: 113 AN XY: 607130

Gnomad4 AFR exome AF: 0.000115

Gnomad4 AMR exome AF: 0.000606

Gnomad4 ASJ exome AF: 0.000218

Gnomad4 EAS exome AF: 0.000127

Gnomad4 SAS exome AF: 0.000839

Gnomad4 FIN exome AF: 0.000185

Gnomad4 NFE exome AF: 0.000108

Gnomad4 OTH exome AF: 0.000200

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000136 AC: 11 AN: 80636 Hom.: 0 Cov.: 17 AF XY: 0.0000769 AC XY: 3 AN XY: 39020

Gnomad4 AFR AF: 0.000103

Gnomad4 AMR AF: 0.000276

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000309

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000153

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00225 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	5.9
DANN	Benign	0.56

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: rs775304849; hg19: chr17-8215396;