Variant rs138521691 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_173728.4(ARHGEF15):c.618C>T(p.Cys206=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00224 in 1,579,228 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0023 ( 5 hom. )

Consequence

ARHGEF15
NM_173728.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.309

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 17-8312938-C-T is Benign according to our data. Variant chr17-8312938-C-T is described in ClinVar as [Benign]. Clinvar id is 412672.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.309 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF15	NM_173728.4 linkuse as main transcript	c.618C>T	p.Cys206=	synonymous_variant	3/16	ENST00000361926.8	NP_776089.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ARHGEF15	ENST00000361926.8 linkuse as main transcript	c.618C>T	p.Cys206=	synonymous_variant	3/16	1	NM_173728.4	ENSP00000355026	P1
ARHGEF15	ENST00000421050.2 linkuse as main transcript	c.618C>T	p.Cys206=	synonymous_variant	3/16	1		ENSP00000412505	P1
ARHGEF15	ENST00000579439.5 linkuse as main transcript	c.618C>T	p.Cys206=	synonymous_variant	3/3	5		ENSP00000464540
ARHGEF15	ENST00000455564.3 linkuse as main transcript	n.1012C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.00154

AC:

234

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.000942

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00265

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00140

AC:

305

AN:

218596

Hom.:

AF XY:

0.00147

AC XY:

172

AN XY:

117286

show subpopulations

Gnomad AFR exome

AF:

0.000196

Gnomad AMR exome

AF:

0.000806

Gnomad ASJ exome

AF:

0.000142

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00176

Gnomad FIN exome

AF:

0.00117

Gnomad NFE exome

AF:

0.00202

Gnomad OTH exome

AF:

0.00224

GnomAD4 exome

AF:

0.00231

AC:

3295

AN:

1426980

Hom.:

Cov.:

AF XY:

0.00226

AC XY:

1598

AN XY:

705748

show subpopulations

Gnomad4 AFR exome

AF:

0.000273

Gnomad4 AMR exome

AF:

0.000941

Gnomad4 ASJ exome

AF:

0.000214

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00169

Gnomad4 FIN exome

AF:

0.00101

Gnomad4 NFE exome

AF:

0.00271

Gnomad4 OTH exome

AF:

0.00142

GnomAD4 genome

AF:

0.00154

AC:

235

AN:

152248

Hom.:

Cov.:

AF XY:

0.00136

AC XY:

101

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.000481

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.000942

Gnomad4 NFE

AF:

0.00265

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00161

Hom.:

Bravo

AF:

0.00136

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Early infantile epileptic encephalopathy with suppression bursts

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 24, 2024

- -

ARHGEF15-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 04, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

5.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over