Variant 17-8312515-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_173728.4(ARHGEF15):c.476G>C(p.Gly159Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000745 in 1,611,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000053 ( 0 hom. )

Consequence

ARHGEF15
NM_173728.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.25

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.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.039922416).

BP6

Variant 17-8312515-G-C is Benign according to our data. Variant chr17-8312515-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 461437.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.476G>C	p.Gly159Ala	missense_variant	2/16	ENST00000361926.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ARHGEF15	ENST00000361926.8 linkuse as main transcript	c.476G>C	p.Gly159Ala	missense_variant	2/16	1	NM_173728.4	P1
ARHGEF15	ENST00000421050.2 linkuse as main transcript	c.476G>C	p.Gly159Ala	missense_variant	2/16	1		P1
ARHGEF15	ENST00000579439.5 linkuse as main transcript	c.476G>C	p.Gly159Ala	missense_variant	2/3	5
ARHGEF15	ENST00000455564.3 linkuse as main transcript	n.589G>C		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.000283

AC:

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000942

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.0000808

AC:

AN:

247474

Hom.:

AF XY:

0.0000598

AC XY:

AN XY:

133876

show subpopulations

Gnomad AFR exome

AF:

0.000806

Gnomad AMR exome

AF:

0.0000880

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000661

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000179

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000528

AC:

AN:

1459668

Hom.:

Cov.:

AF XY:

0.0000565

AC XY:

AN XY:

726084

show subpopulations

Gnomad4 AFR exome

AF:

0.00123

Gnomad4 AMR exome

AF:

0.0000900

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000814

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000144

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000283

AC:

AN:

152104

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.000942

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000955

Alfa

AF:

0.0000126

Hom.:

Bravo

AF:

0.000261

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000741

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

Labcorp Genetics (formerly Invitae), Labcorp

Aug 24, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.70

DEOGEN2

Benign

0.028

T;.;T

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.64

.;T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.040

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

0.51

N;.;N

REVEL

Benign

0.13

Sift

Benign

0.16

T;.;T

Sift4G

Benign

0.77

T;T;T

Polyphen

0.0010

B;.;B

Vest4

0.18

MVP

0.52

MPC

0.090

ClinPred

0.012

GERP RS

3.5

Varity_R

0.062

gMVP

0.094

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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