rs1155226

Variant names:

• chr5-142790609-T-C
• rs1155226
• NM_001135608.3:c.154+19694T>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.154+19694T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,164 control chromosomes in the GnomAD database, including 8,496 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 0.24 (8496 hom., cov: 32)
• Consequence: ARHGAP26 NM_001135608.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.178
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP26	NM_001135608.3	c.154+19694T>C		intron_variant	Intron 1 of 22	ENST00000645722.2	NP_001129080.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP26	ENST00000645722.2	c.154+19694T>C		intron_variant	Intron 1 of 22		NM_001135608.3	ENSP00000495131.1
ARHGAP26	ENST00000274498.9	c.154+19694T>C		intron_variant	Intron 1 of 22	1		ENSP00000274498.4
ARHGAP26	ENST00000642734.1	c.46+19234T>C		intron_variant	Intron 1 of 21			ENSP00000495827.1
ARHGAP26	ENST00000378013.2	n.134+17759T>C		intron_variant	Intron 1 of 5	4

Frequencies

GnomAD3 genomes AF: 0.237 AC: 35987 AN: 152046 Hom.: 8442 Cov.: 32

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.0694

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.0683

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.0820

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.237 AC: 36101 AN: 152164 Hom.: 8496 Cov.: 32 AF XY: 0.231 AC XY: 17195 AN XY: 74408

African (AFR) AF: 0.615 AC: 25483 AN: 41468

American (AMR) AF: 0.126 AC: 1932 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 350 AN: 3466

East Asian (EAS) AF: 0.168 AC: 869 AN: 5166

South Asian (SAS) AF: 0.132 AC: 637 AN: 4822

European-Finnish (FIN) AF: 0.0683 AC: 725 AN: 10616

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.0820 AC: 5579 AN: 68014

Other (OTH) AF: 0.200 AC: 422 AN: 2114

Alfa AF: 0.138 Hom.: 3833

Bravo AF: 0.261

Asia WGS AF: 0.179 AC: 624 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.5
DANN	Benign	0.67
PhyloP100		0.18
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: rs1155226; hg19: chr5-142170174;