17-8318599-G-C

Position:

• chr17-8318599-G-C

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_173728.4(ARHGEF15):​c.1809G>C​(p.Gly603Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000448 in 1,613,896 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00044 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00045 (3 hom.)
• Consequence: ARHGEF15 NM_173728.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.500

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]

ENSG00000226871 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 17-8318599-G-C is Benign according to our data. Variant chr17-8318599-G-C is described in ClinVar as [Benign]. Clinvar id is 412682.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.5 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF15	NM_173728.4	c.1809G>C	p.Gly603Gly	synonymous_variant	11/16	ENST00000361926.8	NP_776089.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF15	ENST00000361926.8	c.1809G>C	p.Gly603Gly	synonymous_variant	11/16	1	NM_173728.4	ENSP00000355026.3
ARHGEF15	ENST00000421050.2	c.1809G>C	p.Gly603Gly	synonymous_variant	11/16	1		ENSP00000412505.1
ARHGEF15	ENST00000647883.1	c.1272G>C	p.Gly424Gly	synonymous_variant	8/13			ENSP00000498197.1
ENSG00000226871	ENST00000458568.1	n.114C>G		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes AF: 0.000440 AC: 67 AN: 152174 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.000866

Gnomad EAS AF: 0.0104

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000872 AC: 219 AN: 251220 Hom.: 0 AF XY: 0.000736 AC XY: 100 AN XY: 135798

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00129

Gnomad EAS exome AF: 0.00990

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000176

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000449 AC: 656 AN: 1461604 Hom.: 3 Cov.: 32 AF XY: 0.000420 AC XY: 305 AN XY: 727046

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00103

Gnomad4 EAS exome AF: 0.0122

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000105

Gnomad4 OTH exome AF: 0.000381

GnomAD4 genome AF: 0.000440 AC: 67 AN: 152292 Hom.: 0 Cov.: 32 AF XY: 0.000564 AC XY: 42 AN XY: 74466

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.000866

Gnomad4 EAS AF: 0.0104

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000201 Hom.: 0

Bravo AF: 0.000468

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Early infantile epileptic encephalopathy with suppression bursts Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 19, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	13
DANN	Benign	0.73

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: rs116091376; hg19: chr17-8221917;