Variant 5-143041850-T-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.1245T>G(p.Gly415=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.982 in 1,604,490 control chromosomes in the GnomAD database, including 778,556 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.98 ( 73127 hom., cov: 30)

Exomes 𝑓: 0.98 ( 705429 hom. )

Consequence

ARHGAP26
NM_001135608.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.02

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=-0.5).

BP6

Variant 5-143041850-T-G is Benign according to our data. Variant chr5-143041850-T-G is described in ClinVar as [Benign]. Clinvar id is 3060469.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-143041850-T-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.02 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.992 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.1245T>G	p.Gly415=	synonymous_variant	14/23	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.1245T>G	p.Gly415=	synonymous_variant	14/23		NM_001135608.3	ENSP00000495131	P1	Q9UNA1-2

Frequencies

GnomAD3 genomes

AF:

0.976

AC:

148458

AN:

152078

Hom.:

73062

Cov.:

show subpopulations

Gnomad AFR

AF:

0.997

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.959

Gnomad ASJ

AF:

0.994

Gnomad EAS

AF:

0.528

Gnomad SAS

AF:

0.978

Gnomad FIN

AF:

0.986

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

0.998

Gnomad OTH

AF:

0.975

GnomAD3 exomes

AF:

0.950

AC:

224440

AN:

236170

Hom.:

108529

AF XY:

0.955

AC XY:

121288

AN XY:

126968

show subpopulations

Gnomad AFR exome

AF:

0.997

Gnomad AMR exome

AF:

0.934

Gnomad ASJ exome

AF:

0.994

Gnomad EAS exome

AF:

0.509

Gnomad SAS exome

AF:

0.988

Gnomad FIN exome

AF:

0.988

Gnomad NFE exome

AF:

0.999

Gnomad OTH exome

AF:

0.974

GnomAD4 exome

AF:

0.983

AC:

1427298

AN:

1452294

Hom.:

705429

Cov.:

AF XY:

0.983

AC XY:

709255

AN XY:

721306

show subpopulations

Gnomad4 AFR exome

AF:

0.998

Gnomad4 AMR exome

AF:

0.935

Gnomad4 ASJ exome

AF:

0.995

Gnomad4 EAS exome

AF:

0.554

Gnomad4 SAS exome

AF:

0.987

Gnomad4 FIN exome

AF:

0.987

Gnomad4 NFE exome

AF:

0.999

Gnomad4 OTH exome

AF:

0.971

GnomAD4 genome

AF:

0.976

AC:

148583

AN:

152196

Hom.:

73127

Cov.:

AF XY:

0.973

AC XY:

72380

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.997

Gnomad4 AMR

AF:

0.959

Gnomad4 ASJ

AF:

0.994

Gnomad4 EAS

AF:

0.528

Gnomad4 SAS

AF:

0.978

Gnomad4 FIN

AF:

0.986

Gnomad4 NFE

AF:

0.998

Gnomad4 OTH

AF:

0.976

Alfa

AF:

0.994

Hom.:

79454

Bravo

AF:

0.971

Asia WGS

AF:

0.807

AC:

2809

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

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

-0.50

CADD

Benign

DANN

Benign

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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