Variant rs767689418 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4BS1

The NM_001367823.1(ARHGEF18):c.3196G>C(p.Glu1066Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000942 in 1,380,464 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000094 ( 0 hom. )

Consequence

ARHGEF18
NM_001367823.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.82

Variant links:

Genes affected

ARHGEF18 (HGNC:17090): (Rho/Rac guanine nucleotide exchange factor 18) Rho GTPases are GTP binding proteins that regulate a wide spectrum of cellular functions. These cellular processes include cytoskeletal rearrangements, gene transcription, cell growth and motility. Activation of Rho GTPases is under the direct control of guanine nucleotide exchange factors (GEFs). The protein encoded by this gene is a guanine nucleotide exchange factor and belongs to the Rho GTPase GEF family. Family members share a common feature, a Dbl (DH) homology domain followed by a pleckstrin (PH) homology domain. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Nov 2018]

ARHGEF18 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3479829).

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00000942 (13/1380464) while in subpopulation SAS AF= 0.000152 (12/79078). AF 95% confidence interval is 0.0000867. There are 0 homozygotes in gnomad4_exome. There are 12 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF18	NM_001367823.1 linkuse as main transcript	c.3196G>C	p.Glu1066Gln	missense_variant	26/29	ENST00000668164.2	NP_001354752.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF18	ENST00000668164.2 linkuse as main transcript	c.3196G>C	p.Glu1066Gln	missense_variant	26/29		NM_001367823.1	ENSP00000499655	A2	Q6ZSZ5-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000385

AC:

AN:

129904

Hom.:

AF XY:

0.0000704

AC XY:

AN XY:

71072

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000223

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000942

AC:

AN:

1380464

Hom.:

Cov.:

AF XY:

0.0000176

AC XY:

AN XY:

681154

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000152

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000173

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000156

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.27

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Pathogenic

0.78

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.84

T;T

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.35

T;T

MetaSVM

Benign

-0.58

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-2.2

N;N

REVEL

Benign

0.25

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.058

T;T

Polyphen

0.91

P;.

Vest4

0.52

MutPred

0.29

.;Loss of solvent accessibility (P = 0.0703);

MVP

0.099

MPC

2.8

ClinPred

0.73

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.69

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over