NM_001135608.3:c.1538+19465A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001135608.3(ARHGAP26):​c.1538+19465A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0254 in 152,268 control chromosomes in the GnomAD database, including 158 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 0.025 ( 158 hom., cov: 32)

Consequence

ARHGAP26
NM_001135608.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.647

Publications

1 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

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=-0.87).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0827 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ARHGAP26NM_001135608.3 linkc.1538+19465A>G intron_variant Intron 17 of 22 ENST00000645722.2 NP_001129080.1 Q9UNA1-2A0A0S2Z536

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ARHGAP26ENST00000645722.2 linkc.1538+19465A>G intron_variant Intron 17 of 22 NM_001135608.3 ENSP00000495131.1 Q9UNA1-2

Frequencies

GnomAD3 genomes
AF:
0.0253
AC:
3850
AN:
152150
Hom.:
155
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0669
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00929
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0824
Gnomad SAS
AF:
0.0894
Gnomad FIN
AF:
0.000189
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000559
Gnomad OTH
AF:
0.0181
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0254
AC:
3866
AN:
152268
Hom.:
158
Cov.:
32
AF XY:
0.0262
AC XY:
1951
AN XY:
74458
show subpopulations
African (AFR)
AF:
0.0668
AC:
2775
AN:
41542
American (AMR)
AF:
0.00928
AC:
142
AN:
15298
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.0822
AC:
425
AN:
5170
South Asian (SAS)
AF:
0.0896
AC:
433
AN:
4830
European-Finnish (FIN)
AF:
0.000189
AC:
2
AN:
10610
Middle Eastern (MID)
AF:
0.00340
AC:
1
AN:
294
European-Non Finnish (NFE)
AF:
0.000544
AC:
37
AN:
68026
Other (OTH)
AF:
0.0241
AC:
51
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
178
355
533
710
888
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
54
108
162
216
270
<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:
0.00820
Hom.:
41
Bravo
AF:
0.0264
Asia WGS
AF:
0.110
AC:
382
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
3.1
DANN
Benign
0.50
PhyloP100
-0.65
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs17099857; hg19: chr5-142456777; API