Variant 7-144363761-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_005435.4(ARHGEF5):c.1092A>C(p.Ile364=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0021 ( 3 hom., cov: 20)

Exomes 𝑓: 0.00030 ( 14 hom. )

Failed GnomAD Quality Control

Consequence

ARHGEF5
NM_005435.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.94

Variant links:

Genes affected

ARHGEF5 (HGNC:13209): (Rho guanine nucleotide exchange factor 5) Rho GTPases play a fundamental role in numerous cellular processes initiated by extracellular stimuli that work through G protein coupled receptors. The encoded protein may form a complex with G proteins and stimulate Rho-dependent signals. This protein may be involved in the control of cytoskeletal organization. [provided by RefSeq, Jul 2008]

ARHGEF5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.03).

BP6

Variant 7-144363761-A-C is Benign according to our data. Variant chr7-144363761-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2658127.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.94 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF5	NM_005435.4 linkuse as main transcript	c.1092A>C	p.Ile364=	synonymous_variant	2/15	ENST00000056217.10	NP_005426.2
ARHGEF5	XM_017012623.3 linkuse as main transcript	c.1092A>C	p.Ile364=	synonymous_variant	2/6		XP_016868112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF5	ENST00000056217.10 linkuse as main transcript	c.1092A>C	p.Ile364=	synonymous_variant	2/15	1	NM_005435.4	ENSP00000056217	P1	Q12774-1
ARHGEF5	ENST00000498580.5 linkuse as main transcript	c.184+908A>C		intron_variant		3		ENSP00000417979

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

288

AN:

134306

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00744

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000368

Gnomad ASJ

AF:

0.000311

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000229

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000505

Gnomad OTH

AF:

0.00272

GnomAD3 exomes

AF:

0.000912

AC:

AN:

71246

Hom.:

AF XY:

0.000860

AC XY:

AN XY:

34898

show subpopulations

Gnomad AFR exome

AF:

0.00980

Gnomad AMR exome

AF:

0.000277

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000110

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000302

AC:

420

AN:

1389166

Hom.:

Cov.:

AF XY:

0.000293

AC XY:

203

AN XY:

692404

show subpopulations

Gnomad4 AFR exome

AF:

0.00991

Gnomad4 AMR exome

AF:

0.000299

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000471

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000305

Gnomad4 OTH exome

AF:

0.000846

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00214

AC:

287

AN:

134406

Hom.:

Cov.:

AF XY:

0.00203

AC XY:

133

AN XY:

65492

show subpopulations

Gnomad4 AFR

AF:

0.00742

Gnomad4 AMR

AF:

0.000367

Gnomad4 ASJ

AF:

0.000311

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000505

Gnomad4 OTH

AF:

0.00269

Alfa

AF:

0.00179

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2023

ARHGEF5: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.26

DANN

Benign

0.48

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