dbSNP rs27779: ARHGAP26:c.384+73C>A (chr5-142879518-C-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_001135608.3(ARHGAP26):c.384+73C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 1,353,670 control chromosomes in the GnomAD database, including 87,416 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 0.43 ( 16907 hom., cov: 32)

Exomes 𝑓: 0.32 ( 70509 hom. )

Consequence

ARHGAP26
NM_001135608.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.813

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

juvenile myelomonocytic leukemia
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Ambry Genetics

ARHGAP26 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=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP26	NM_001135608.3 link	c.384+73C>A		intron_variant	Intron 4 of 22	ENST00000645722.2	NP_001129080.1	Q9UNA1-2A0A0S2Z536

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP26	ENST00000645722.2 link	c.384+73C>A		intron_variant	Intron 4 of 22		NM_001135608.3	ENSP00000495131.1		Q9UNA1-2

Frequencies

GnomAD3 genomes

AF:

0.426

AC:

64679

AN:

151922

Hom.:

16861

Cov.:

show subpopulations

Gnomad AFR

AF:

0.684

Gnomad AMI

AF:

0.274

Gnomad AMR

AF:

0.420

Gnomad ASJ

AF:

0.312

Gnomad EAS

AF:

0.819

Gnomad SAS

AF:

0.573

Gnomad FIN

AF:

0.281

Gnomad MID

AF:

0.323

Gnomad NFE

AF:

0.261

Gnomad OTH

AF:

0.399

GnomAD4 exome

AF:

0.316

AC:

379954

AN:

1201630

Hom.:

70509

AF XY:

0.321

AC XY:

192255

AN XY:

599038

show subpopulations

African (AFR)

AF:

0.702

AC:

18359

AN:

26158

American (AMR)

AF:

0.489

AC:

13035

AN:

26630

Ashkenazi Jewish (ASJ)

AF:

0.299

AC:

5914

AN:

19794

East Asian (EAS)

AF:

0.803

AC:

29294

AN:

36494

South Asian (SAS)

AF:

0.548

AC:

37157

AN:

67836

European-Finnish (FIN)

AF:

0.275

AC:

13737

AN:

49912

Middle Eastern (MID)

AF:

0.421

AC:

2132

AN:

5062

European-Non Finnish (NFE)

AF:

0.263

AC:

241992

AN:

918962

Other (OTH)

AF:

0.361

AC:

18334

AN:

50782

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

11059

22118

33177

44236

55295

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8458

16916

25374

33832

42290

<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:

0.426

AC:

64789

AN:

152040

Hom.:

16907

Cov.:

AF XY:

0.431

AC XY:

32020

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.684

AC:

28361

AN:

41452

American (AMR)

AF:

0.421

AC:

6429

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.312

AC:

1080

AN:

3464

East Asian (EAS)

AF:

0.819

AC:

4240

AN:

5174

South Asian (SAS)

AF:

0.572

AC:

2755

AN:

4820

European-Finnish (FIN)

AF:

0.281

AC:

2966

AN:

10550

Middle Eastern (MID)

AF:

0.340

AC:

100

AN:

294

European-Non Finnish (NFE)

AF:

0.261

AC:

17766

AN:

67984

Other (OTH)

AF:

0.399

AC:

843

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1588

3175

4763

6350

7938

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

584

1168

1752

2336

2920

<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:

0.285

Hom.:

4192

Bravo

AF:

0.451

Asia WGS

AF:

0.688

AC:

2390

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.24

(source)

DANN

Benign

0.77

PhyloP100

-0.81

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over