Genetic Variant ARHGEF25:c.553-121G>A (chr12-57613895-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_182947.4(ARHGEF25):c.553-121G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 1,463,824 control chromosomes in the GnomAD database, including 35,749 homozygotes. 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: 𝑓 0.17 ( 2652 hom., cov: 31)

Exomes 𝑓: 0.22 ( 33097 hom. )

Consequence

ARHGEF25
NM_182947.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.101

Publications

6 publications found

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:41260):

ENSG00000224713 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182947.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ARHGEF25	NM_182947.4	MANE Select	c.553-121G>A	intron	N/A	NP_891992.3
ARHGEF25	NM_001111270.3		c.670-121G>A	intron	N/A	NP_001104740.2
ARHGEF25	NM_001347933.2		c.553-121G>A	intron	N/A	NP_001334862.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ARHGEF25	ENST00000286494.9	TSL:1 MANE Select	c.553-121G>A	intron	N/A	ENSP00000286494.4
ARHGEF25	ENST00000333972.11	TSL:1	c.670-121G>A	intron	N/A	ENSP00000335560.7
ENSG00000224713	ENST00000444467.2	TSL:1	n.839-186C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.168

AC:

25463

AN:

151806

Hom.:

2651

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0413

Gnomad AMI

AF:

0.199

Gnomad AMR

AF:

0.152

Gnomad ASJ

AF:

0.182

Gnomad EAS

AF:

0.175

Gnomad SAS

AF:

0.159

Gnomad FIN

AF:

0.259

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.232

Gnomad OTH

AF:

0.191

GnomAD4 exome

AF:

0.219

AC:

286935

AN:

1311900

Hom.:

33097

Cov.:

AF XY:

0.217

AC XY:

141966

AN XY:

654696

show subpopulations

African (AFR)

AF:

0.0358

AC:

1097

AN:

30614

American (AMR)

AF:

0.136

AC:

5591

AN:

41256

Ashkenazi Jewish (ASJ)

AF:

0.196

AC:

4486

AN:

22886

East Asian (EAS)

AF:

0.185

AC:

7188

AN:

38874

South Asian (SAS)

AF:

0.148

AC:

11514

AN:

77816

European-Finnish (FIN)

AF:

0.261

AC:

13464

AN:

51592

Middle Eastern (MID)

AF:

0.181

AC:

819

AN:

4522

European-Non Finnish (NFE)

AF:

0.234

AC:

231627

AN:

989380

Other (OTH)

AF:

0.203

AC:

11149

AN:

54960

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

11730

23459

35189

46918

58648

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7548

15096

22644

30192

37740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.168

AC:

25471

AN:

151924

Hom.:

2652

Cov.:

AF XY:

0.169

AC XY:

12513

AN XY:

74248

show subpopulations

African (AFR)

AF:

0.0413

AC:

1711

AN:

41462

American (AMR)

AF:

0.152

AC:

2323

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.182

AC:

632

AN:

3466

East Asian (EAS)

AF:

0.175

AC:

897

AN:

5138

South Asian (SAS)

AF:

0.159

AC:

763

AN:

4798

European-Finnish (FIN)

AF:

0.259

AC:

2735

AN:

10570

Middle Eastern (MID)

AF:

0.180

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.232

AC:

15767

AN:

67916

Other (OTH)

AF:

0.194

AC:

409

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1014

2027

3041

4054

5068

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

272

544

816

1088

1360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.152

Hom.:

454

Bravo

AF:

0.155

Asia WGS

AF:

0.160

AC:

560

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.0

(source)

DANN

Benign

0.85

PhyloP100

0.10

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over