Genetic Variant NM_001135608.3:c.2191+3637C>T (chr5-143217725-C-T) – 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.2191+3637C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,180 control chromosomes in the GnomAD database, including 3,464 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 0.19 ( 3464 hom., cov: 32)

Consequence

ARHGAP26
NM_001135608.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.403

Publications

2 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:

LOC124901099 (HGNC:):

LOC124901099 links:

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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=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135608.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ARHGAP26	NM_001135608.3	MANE Select	c.2191+3637C>T	intron	N/A	NP_001129080.1
ARHGAP26	NM_015071.6		c.2356+3637C>T	intron	N/A	NP_055886.1
ARHGAP26	NM_001349547.2		c.1972+3637C>T	intron	N/A	NP_001336476.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ARHGAP26	ENST00000645722.2	MANE Select	c.2191+3637C>T	intron	N/A	ENSP00000495131.1
ARHGAP26	ENST00000274498.9	TSL:1	c.2356+3637C>T	intron	N/A	ENSP00000274498.4
ARHGAP26	ENST00000418236.5	TSL:1	c.793+3637C>T	intron	N/A	ENSP00000416889.1

Frequencies

GnomAD3 genomes

AF:

0.191

AC:

28976

AN:

152062

Hom.:

3466

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0511

Gnomad AMI

AF:

0.158

Gnomad AMR

AF:

0.218

Gnomad ASJ

AF:

0.253

Gnomad EAS

AF:

0.412

Gnomad SAS

AF:

0.206

Gnomad FIN

AF:

0.300

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.230

Gnomad OTH

AF:

0.217

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.190

AC:

28960

AN:

152180

Hom.:

3464

Cov.:

AF XY:

0.197

AC XY:

14652

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.0510

AC:

2118

AN:

41530

American (AMR)

AF:

0.218

AC:

3333

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.253

AC:

878

AN:

3472

East Asian (EAS)

AF:

0.412

AC:

2132

AN:

5176

South Asian (SAS)

AF:

0.206

AC:

991

AN:

4822

European-Finnish (FIN)

AF:

0.300

AC:

3175

AN:

10580

Middle Eastern (MID)

AF:

0.286

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.230

AC:

15649

AN:

67990

Other (OTH)

AF:

0.216

AC:

456

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1167

2333

3500

4666

5833

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

308

616

924

1232

1540

<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:

0.202

Hom.:

5106

Bravo

AF:

0.177

Asia WGS

AF:

0.280

AC:

975

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.1

(source)

DANN

Benign

0.45

PhyloP100

0.40

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over