Variant rs35204656 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_173728.4(ARHGEF15):c.1827A>G(p.Glu609=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0159 in 1,613,772 control chromosomes in the GnomAD database, including 264 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 24 hom., cov: 32)

Exomes 𝑓: 0.016 ( 240 hom. )

Consequence

ARHGEF15
NM_173728.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.34

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 17-8318617-A-G is Benign according to our data. Variant chr17-8318617-A-G is described in ClinVar as [Benign]. Clinvar id is 412671.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.34 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF15	NM_173728.4 linkuse as main transcript	c.1827A>G	p.Glu609=	synonymous_variant	11/16	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.1827A>G	p.Glu609=	synonymous_variant	11/16	1	NM_173728.4	ENSP00000355026	P1
ARHGEF15	ENST00000421050.2 linkuse as main transcript	c.1827A>G	p.Glu609=	synonymous_variant	11/16	1		ENSP00000412505	P1
	ENST00000458568.1 linkuse as main transcript	n.96T>C		non_coding_transcript_exon_variant	1/2	3
ARHGEF15	ENST00000647883.1 linkuse as main transcript	c.1290A>G	p.Glu430=	synonymous_variant	8/13			ENSP00000498197

Frequencies

GnomAD3 genomes

AF:

0.0142

AC:

2157

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00398

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0191

Gnomad ASJ

AF:

0.0392

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00455

Gnomad FIN

AF:

0.0237

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0181

Gnomad OTH

AF:

0.0201

GnomAD3 exomes

AF:

0.0149

AC:

3740

AN:

251206

Hom.:

AF XY:

0.0150

AC XY:

2032

AN XY:

135780

show subpopulations

Gnomad AFR exome

AF:

0.00326

Gnomad AMR exome

AF:

0.0144

Gnomad ASJ exome

AF:

0.0430

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00467

Gnomad FIN exome

AF:

0.0200

Gnomad NFE exome

AF:

0.0180

Gnomad OTH exome

AF:

0.0216

GnomAD4 exome

AF:

0.0161

AC:

23544

AN:

1461540

Hom.:

240

Cov.:

AF XY:

0.0161

AC XY:

11688

AN XY:

727010

show subpopulations

Gnomad4 AFR exome

AF:

0.00568

Gnomad4 AMR exome

AF:

0.0157

Gnomad4 ASJ exome

AF:

0.0450

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00546

Gnomad4 FIN exome

AF:

0.0185

Gnomad4 NFE exome

AF:

0.0167

Gnomad4 OTH exome

AF:

0.0190

GnomAD4 genome

AF:

0.0142

AC:

2155

AN:

152232

Hom.:

Cov.:

AF XY:

0.0142

AC XY:

1058

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.00397

Gnomad4 AMR

AF:

0.0190

Gnomad4 ASJ

AF:

0.0392

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00435

Gnomad4 FIN

AF:

0.0237

Gnomad4 NFE

AF:

0.0181

Gnomad4 OTH

AF:

0.0204

Alfa

AF:

0.0176

Hom.:

Bravo

AF:

0.0141

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0213

EpiControl

AF:

0.0210

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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 30, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.76

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