Variant 5-142771377-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001349547.2(ARHGAP26):c.46+2T>C variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 1,231,858 control chromosomes in the GnomAD database, including 28,865 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.31 ( 13941 hom., cov: 33)

Exomes 𝑓: 0.12 ( 14924 hom. )

Consequence

ARHGAP26
NM_001349547.2 splice_donor, intron

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.00700

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:

ARHGAP26 (HGNC:):

ARHGAP26 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 5-142771377-T-C is Benign according to our data. Variant chr5-142771377-T-C is described in ClinVar as [Benign]. Clinvar id is 3055505.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.763 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.154+462T>C		intron_variant		ENST00000645722.2	NP_001129080.1	Q9UNA1-2A0A0S2Z536

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
ARHGAP26	ENST00000645722.2 linkuse as main transcript	c.154+462T>C	intron_variant		NM_001135608.3	ENSP00000495131.1	Q9UNA1-2
ARHGAP26	ENST00000274498.9 linkuse as main transcript	c.154+462T>C	intron_variant	1		ENSP00000274498.4	Q9UNA1-1
ARHGAP26	ENST00000642734.1 linkuse as main transcript	c.46+2T>C	splice_donor_variant, intron_variant			ENSP00000495827.1	A0A2R8YGB3

Frequencies

GnomAD3 genomes

AF:

0.314

AC:

47692

AN:

151920

Hom.:

13892

Cov.:

show subpopulations

Gnomad AFR

AF:

0.770

Gnomad AMI

AF:

0.0439

Gnomad AMR

AF:

0.268

Gnomad ASJ

AF:

0.139

Gnomad EAS

AF:

0.366

Gnomad SAS

AF:

0.223

Gnomad FIN

AF:

0.134

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.0912

Gnomad OTH

AF:

0.284

GnomAD4 exome

AF:

0.118

AC:

127768

AN:

1079820

Hom.:

14924

Cov.:

AF XY:

0.117

AC XY:

59396

AN XY:

509798

show subpopulations

Gnomad4 AFR exome

AF:

0.804

Gnomad4 AMR exome

AF:

0.267

Gnomad4 ASJ exome

AF:

0.149

Gnomad4 EAS exome

AF:

0.351

Gnomad4 SAS exome

AF:

0.210

Gnomad4 FIN exome

AF:

0.131

Gnomad4 NFE exome

AF:

0.0871

Gnomad4 OTH exome

AF:

0.179

GnomAD4 genome

AF:

0.314

AC:

47792

AN:

152038

Hom.:

13941

Cov.:

AF XY:

0.313

AC XY:

23282

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.770

Gnomad4 AMR

AF:

0.268

Gnomad4 ASJ

AF:

0.139

Gnomad4 EAS

AF:

0.366

Gnomad4 SAS

AF:

0.222

Gnomad4 FIN

AF:

0.134

Gnomad4 NFE

AF:

0.0912

Gnomad4 OTH

AF:

0.284

Alfa

AF:

0.210

Hom.:

1033

Bravo

AF:

0.348

TwinsUK

AF:

0.0914

AC:

339

ALSPAC

AF:

0.0934

AC:

360

Asia WGS

AF:

0.347

AC:

1207

AN:

3478

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

May 10, 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

-0.87

CADD

Benign

DANN

Benign

0.70

FATHMM_MKL

Benign

0.00098

GERP RS

2.5

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