Variant 17-8316081-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_ModerateBP6_Moderate

The NM_173728.4(ARHGEF15):c.1637G>C(p.Arg546Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00125 in 1,602,988 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. R546R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00093 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0013 ( 2 hom. )

Consequence

ARHGEF15
NM_173728.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.58

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.076511025).

BP6

Variant 17-8316081-G-C is Benign according to our data. Variant chr17-8316081-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 461427.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF15	NM_173728.4 linkuse as main transcript	c.1637G>C	p.Arg546Pro	missense_variant	9/16	ENST00000361926.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ARHGEF15	ENST00000361926.8 linkuse as main transcript	c.1637G>C	p.Arg546Pro	missense_variant	9/16	1	NM_173728.4	P1
ARHGEF15	ENST00000421050.2 linkuse as main transcript	c.1637G>C	p.Arg546Pro	missense_variant	9/16	1		P1
ARHGEF15	ENST00000647883.1 linkuse as main transcript	c.1100G>C	p.Arg367Pro	missense_variant	6/13

Frequencies

GnomAD3 genomes

AF:

0.000933

AC:

142

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000651

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000712

AC:

167

AN:

234688

Hom.:

AF XY:

0.000752

AC XY:

AN XY:

128918

show subpopulations

Gnomad AFR exome

AF:

0.000544

Gnomad AMR exome

AF:

0.0000885

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000663

Gnomad FIN exome

AF:

0.000275

Gnomad NFE exome

AF:

0.00135

Gnomad OTH exome

AF:

0.000683

GnomAD4 exome

AF:

0.00129

AC:

1865

AN:

1450688

Hom.:

Cov.:

AF XY:

0.00125

AC XY:

903

AN XY:

721996

show subpopulations

Gnomad4 AFR exome

AF:

0.000150

Gnomad4 AMR exome

AF:

0.0000900

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000931

Gnomad4 FIN exome

AF:

0.000227

Gnomad4 NFE exome

AF:

0.00162

Gnomad4 OTH exome

AF:

0.000598

GnomAD4 genome

AF:

0.000932

AC:

142

AN:

152300

Hom.:

Cov.:

AF XY:

0.000980

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000650

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00112

Hom.:

Bravo

AF:

0.000790

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.000583

AC:

ExAC

AF:

0.000685

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Early infantile epileptic encephalopathy with suppression bursts

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.97

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Uncertain

-0.020

Cadd

Pathogenic

Dann

Uncertain

0.99

DEOGEN2

Uncertain

0.47

T;T;.

Eigen

Benign

0.089

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.90

M_CAP

Benign

0.034

MetaRNN

Benign

0.077

T;T;T

MetaSVM

Benign

-0.67

MutationAssessor

Benign

1.7

L;L;.

MutationTaster

Benign

0.99

D;D

PrimateAI

Uncertain

0.59

PROVEAN

Pathogenic

-5.7

D;D;.

REVEL

Uncertain

0.33

Sift

Benign

0.081

T;T;.

Sift4G

Uncertain

0.0060

D;D;.

Polyphen

0.064

B;B;.

Vest4

0.66

MVP

0.72

MPC

1.6

ClinPred

0.087

GERP RS

3.7

Varity_R

0.75

gMVP

0.79

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