Variant 2-130931014-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001367493.1(ARHGEF4):c.3615G>A(p.Ala1205Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 1,613,538 control chromosomes in the GnomAD database, including 32,266 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.23 ( 4903 hom., cov: 32)

Exomes 𝑓: 0.19 ( 27363 hom. )

Consequence

ARHGEF4
NM_001367493.1 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0670

Variant links:

Genes affected

ARHGEF4 (HGNC:684): (Rho guanine nucleotide exchange factor 4) Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli that work through G protein coupled receptors. The protein encoded by this gene may form complex with G proteins and stimulate Rho-dependent signals. Multiple alternatively spliced transcript variants encoding different isoforms have been found, but the full-length nature of some variants has not been determined. [provided by RefSeq, Jun 2013]

ARHGEF4 links:

ARHGEF4 (HGNC:):

ARHGEF4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 2-130931014-G-A is Benign according to our data. Variant chr2-130931014-G-A is described in ClinVar as [Benign]. Clinvar id is 3058950.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.067 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF4	NM_001367493.1 linkuse as main transcript	c.3615G>A	p.Ala1205Ala	synonymous_variant	3/14	ENST00000409359.7	NP_001354422.1
ARHGEF4	NM_001375900.1 linkuse as main transcript	c.102G>A	p.Ala34Ala	synonymous_variant	2/13		NP_001362829.1
ARHGEF4	NM_015320.4 linkuse as main transcript	c.57G>A	p.Ala19Ala	synonymous_variant	4/15		NP_056135.2	Q9NR80-1Q9NTG0
ARHGEF4	NM_001375901.1 linkuse as main transcript	c.22+35G>A		intron_variant			NP_001362830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF4	ENST00000409359.7 linkuse as main transcript	c.3615G>A	p.Ala1205Ala	synonymous_variant	3/14	5	NM_001367493.1	ENSP00000386794.3		E7EV07

Frequencies

GnomAD3 genomes

AF:

0.233

AC:

35448

AN:

152006

Hom.:

4903

Cov.:

show subpopulations

Gnomad AFR

AF:

0.383

Gnomad AMI

AF:

0.0428

Gnomad AMR

AF:

0.158

Gnomad ASJ

AF:

0.192

Gnomad EAS

AF:

0.139

Gnomad SAS

AF:

0.320

Gnomad FIN

AF:

0.149

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.178

Gnomad OTH

AF:

0.225

GnomAD3 exomes

AF:

0.189

AC:

47156

AN:

249094

Hom.:

5339

AF XY:

0.195

AC XY:

26296

AN XY:

134818

show subpopulations

Gnomad AFR exome

AF:

0.393

Gnomad AMR exome

AF:

0.0939

Gnomad ASJ exome

AF:

0.203

Gnomad EAS exome

AF:

0.129

Gnomad SAS exome

AF:

0.301

Gnomad FIN exome

AF:

0.152

Gnomad NFE exome

AF:

0.175

Gnomad OTH exome

AF:

0.183

GnomAD4 exome

AF:

0.187

AC:

272879

AN:

1461414

Hom.:

27363

Cov.:

AF XY:

0.190

AC XY:

138448

AN XY:

726914

show subpopulations

Gnomad4 AFR exome

AF:

0.392

Gnomad4 AMR exome

AF:

0.100

Gnomad4 ASJ exome

AF:

0.200

Gnomad4 EAS exome

AF:

0.127

Gnomad4 SAS exome

AF:

0.299

Gnomad4 FIN exome

AF:

0.152

Gnomad4 NFE exome

AF:

0.178

Gnomad4 OTH exome

AF:

0.201

GnomAD4 genome

AF:

0.233

AC:

35471

AN:

152124

Hom.:

4903

Cov.:

AF XY:

0.231

AC XY:

17147

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.383

Gnomad4 AMR

AF:

0.157

Gnomad4 ASJ

AF:

0.192

Gnomad4 EAS

AF:

0.139

Gnomad4 SAS

AF:

0.319

Gnomad4 FIN

AF:

0.149

Gnomad4 NFE

AF:

0.178

Gnomad4 OTH

AF:

0.226

Alfa

AF:

0.182

Hom.:

5457

Bravo

AF:

0.233

Asia WGS

AF:

0.226

AC:

785

AN:

3478

EpiCase

AF:

0.182

EpiControl

AF:

0.189

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ARHGEF4-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 24, 2019

This variant is classified as 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

-0.83

CADD

Benign

6.3

DANN

Benign

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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