rs17287593

Variant names:

• chr5-143121863-T-C
• rs17287593
• NM_001135608.3:c.1698+716T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001135608.3(ARHGAP26):​c.1698+716T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0745 in 152,254 control chromosomes in the GnomAD database, including 532 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 0.075 (532 hom., cov: 32)
• Consequence: ARHGAP26 NM_001135608.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.112
• Publications: 3 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP26	NM_001135608.3	c.1698+716T>C		intron_variant	Intron 18 of 22	ENST00000645722.2	NP_001129080.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP26	ENST00000645722.2	c.1698+716T>C		intron_variant	Intron 18 of 22		NM_001135608.3	ENSP00000495131.1

Frequencies

GnomAD3 genomes AF: 0.0745 AC: 11337 AN: 152136 Hom.: 533 Cov.: 32

Gnomad AFR AF: 0.0186

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.0678

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.0509

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.0829

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

GnomAD4 genome AF: 0.0745 AC: 11344 AN: 152254 Hom.: 532 Cov.: 32 AF XY: 0.0727 AC XY: 5414 AN XY: 74440

African (AFR) AF: 0.0186 AC: 771 AN: 41550

American (AMR) AF: 0.0678 AC: 1037 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 473 AN: 3472

East Asian (EAS) AF: 0.129 AC: 667 AN: 5180

South Asian (SAS) AF: 0.148 AC: 714 AN: 4816

European-Finnish (FIN) AF: 0.0509 AC: 541 AN: 10620

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6835 AN: 68006

Other (OTH) AF: 0.0825 AC: 174 AN: 2108

Alfa AF: 0.0765 Hom.: 346

Bravo AF: 0.0717

Asia WGS AF: 0.112 AC: 387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.60
PhyloP100		0.11
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

Other links and lift over

dbSNP: rs17287593; hg19: chr5-142501428; COSMIC: COSV50826024;