Variant 5-142875114-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001135608.3(ARHGAP26):c.255A>G(p.Arg85=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 1,612,584 control chromosomes in the GnomAD database, including 126,814 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.48 ( 21666 hom., cov: 32)

Exomes 𝑓: 0.35 ( 105148 hom. )

Consequence

ARHGAP26
NM_001135608.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.26

Variant links:

Genes affected

ARHGAP26 (HGNC:17073): (Rho GTPase activating protein 26) Interaction of a cell with the extracellular matrix triggers integrin cell surface receptors to begin signaling cascades that regulate the organization of the actin-cytoskeleton. One of the proteins involved in these cascades is focal adhesion kinase. The protein encoded by this gene is a GTPase activating protein that binds to focal adhesion kinase and mediates the activity of the GTP binding proteins RhoA and Cdc42. Defects in this gene are a cause of juvenile myelomonocytic leukemia (JMML). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2017]

ARHGAP26 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=-0.61).

BP6

Variant 5-142875114-A-G is Benign according to our data. Variant chr5-142875114-A-G is described in ClinVar as [Benign]. Clinvar id is 3059213.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-142875114-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.26 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP26	NM_001135608.3 linkuse as main transcript	c.255A>G	p.Arg85=	synonymous_variant	3/23	ENST00000645722.2	NP_001129080.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP26	ENST00000645722.2 linkuse as main transcript	c.255A>G	p.Arg85=	synonymous_variant	3/23		NM_001135608.3	ENSP00000495131	P1	Q9UNA1-2

Frequencies

GnomAD3 genomes

AF:

0.480

AC:

72872

AN:

151950

Hom.:

21605

Cov.:

show subpopulations

Gnomad AFR

AF:

0.794

Gnomad AMI

AF:

0.311

Gnomad AMR

AF:

0.454

Gnomad ASJ

AF:

0.332

Gnomad EAS

AF:

0.863

Gnomad SAS

AF:

0.629

Gnomad FIN

AF:

0.301

Gnomad MID

AF:

0.332

Gnomad NFE

AF:

0.293

Gnomad OTH

AF:

0.456

GnomAD3 exomes

AF:

0.444

AC:

111672

AN:

251336

Hom.:

30144

AF XY:

0.437

AC XY:

59311

AN XY:

135822

show subpopulations

Gnomad AFR exome

AF:

0.805

Gnomad AMR exome

AF:

0.543

Gnomad ASJ exome

AF:

0.327

Gnomad EAS exome

AF:

0.869

Gnomad SAS exome

AF:

0.614

Gnomad FIN exome

AF:

0.297

Gnomad NFE exome

AF:

0.290

Gnomad OTH exome

AF:

0.389

GnomAD4 exome

AF:

0.350

AC:

511089

AN:

1460516

Hom.:

105148

Cov.:

AF XY:

0.356

AC XY:

258411

AN XY:

726606

show subpopulations

Gnomad4 AFR exome

AF:

0.812

Gnomad4 AMR exome

AF:

0.538

Gnomad4 ASJ exome

AF:

0.324

Gnomad4 EAS exome

AF:

0.859

Gnomad4 SAS exome

AF:

0.606

Gnomad4 FIN exome

AF:

0.297

Gnomad4 NFE exome

AF:

0.291

Gnomad4 OTH exome

AF:

0.397

GnomAD4 genome

AF:

0.480

AC:

73001

AN:

152068

Hom.:

21666

Cov.:

AF XY:

0.484

AC XY:

35931

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.795

Gnomad4 AMR

AF:

0.455

Gnomad4 ASJ

AF:

0.332

Gnomad4 EAS

AF:

0.863

Gnomad4 SAS

AF:

0.627

Gnomad4 FIN

AF:

0.301

Gnomad4 NFE

AF:

0.293

Gnomad4 OTH

AF:

0.459

Alfa

AF:

0.336

Hom.:

19394

Bravo

AF:

0.508

Asia WGS

AF:

0.741

AC:

2574

AN:

3478

EpiCase

AF:

0.290

EpiControl

AF:

0.286

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ARHGAP26-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 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

-0.61

CADD

Benign

DANN

Benign

0.57

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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