NM_001135608.3:c.1108-21965A>G

Variant names:

• chr5-142992115-A-G
• rs13172733
• NM_001135608.3:c.1108-21965A>G

Variant summary

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

The NM_001135608.3(ARHGAP26):​c.1108-21965A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 151,838 control chromosomes in the GnomAD database, including 27,912 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 0.56 (27912 hom., cov: 31)
• Consequence: ARHGAP26 NM_001135608.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.923
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.738 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP26	NM_001135608.3	MANE Select	c.1108-21965A>G		intron	N/A	NP_001129080.1
	ARHGAP26	NM_015071.6		c.1108-21965A>G		intron	N/A	NP_055886.1
	ARHGAP26	NM_001349547.2		c.1000-21965A>G		intron	N/A	NP_001336476.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP26	ENST00000645722.2	MANE Select	c.1108-21965A>G		intron	N/A	ENSP00000495131.1
	ARHGAP26	ENST00000274498.9	TSL:1	c.1108-21965A>G		intron	N/A	ENSP00000274498.4
	ARHGAP26	ENST00000642734.1		c.1000-21965A>G		intron	N/A	ENSP00000495827.1

Frequencies

GnomAD3 genomes AF: 0.563 AC: 85352 AN: 151718 Hom.: 27922 Cov.: 31

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.749

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.703

Gnomad EAS AF: 0.0854

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.706

Gnomad MID AF: 0.666

Gnomad NFE AF: 0.744

Gnomad OTH AF: 0.604

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

GnomAD4 genome AF: 0.562 AC: 85347 AN: 151838 Hom.: 27912 Cov.: 31 AF XY: 0.556 AC XY: 41253 AN XY: 74204

African (AFR) AF: 0.274 AC: 11348 AN: 41368

American (AMR) AF: 0.603 AC: 9203 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.703 AC: 2440 AN: 3470

East Asian (EAS) AF: 0.0850 AC: 439 AN: 5166

South Asian (SAS) AF: 0.384 AC: 1847 AN: 4816

European-Finnish (FIN) AF: 0.706 AC: 7422 AN: 10512

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.744 AC: 50514 AN: 67936

Other (OTH) AF: 0.599 AC: 1261 AN: 2106

Alfa AF: 0.617 Hom.: 22412

Bravo AF: 0.538

Asia WGS AF: 0.225 AC: 782 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.5
DANN	Benign	0.54
PhyloP100		0.92
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: rs13172733; hg19: chr5-142371680;