Variant 12-57613338-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_182947.4(ARHGEF25):c.387G>A(p.Glu129Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000471 in 1,614,118 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 (★).

Frequency

Genomes: 𝑓 0.00046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00047 ( 2 hom. )

Consequence

ARHGEF25
NM_182947.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.357

Variant links:

Genes affected

ARHGEF25 (HGNC:30275): (Rho guanine nucleotide exchange factor 25) Rho GTPases alternate between an inactive GDP-bound state and an active GTP-bound state, and GEFs facilitate GDP/GTP exchange. This gene encodes a guanine nucleotide exchange factor (GEF) which interacts with Rho GTPases involved in contraction of vascular smooth muscles, regulation of responses to angiotensin II and lens cell differentiation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

ARHGEF25 links:

ENSG00000224713 (HGNC:):

ENSG00000224713 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 12-57613338-G-A is Benign according to our data. Variant chr12-57613338-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3341581.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.357 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF25	NM_182947.4 linkuse as main transcript	c.387G>A	p.Glu129Glu	synonymous_variant	3/15	ENST00000286494.9	NP_891992.3	Q86VW2-1
ARHGEF25	NM_001111270.3 linkuse as main transcript	c.504G>A	p.Glu168Glu	synonymous_variant	4/16		NP_001104740.2	Q86VW2-3
ARHGEF25	NM_001347933.2 linkuse as main transcript	c.387G>A	p.Glu129Glu	synonymous_variant	3/14		NP_001334862.2	Q86VW2
ARHGEF25	NR_046223.2 linkuse as main transcript	n.877G>A		non_coding_transcript_exon_variant	4/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF25	ENST00000286494.9 linkuse as main transcript	c.387G>A	p.Glu129Glu	synonymous_variant	3/15	1	NM_182947.4	ENSP00000286494.4		Q86VW2-1

Frequencies

GnomAD3 genomes

AF:

0.000460

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000779

AC:

196

AN:

251454

Hom.:

AF XY:

0.000846

AC XY:

115

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00104

Gnomad ASJ exome

AF:

0.00764

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000571

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000472

AC:

690

AN:

1461890

Hom.:

Cov.:

AF XY:

0.000498

AC XY:

362

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.000917

Gnomad4 ASJ exome

AF:

0.00807

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000313

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000282

Gnomad4 OTH exome

AF:

0.00118

GnomAD4 genome

AF:

0.000460

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.000417

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00749

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.00143

Alfa

AF:

0.000991

Hom.:

Bravo

AF:

0.000638

EpiCase

AF:

0.000872

EpiControl

AF:

0.000889

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

Aug 01, 2024

ARHGEF25: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.64

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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