rs13172733

Positions:

• chr5-142992115-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP26	NM_001135608.3	c.1108-21965A>G		intron_variant		ENST00000645722.2	NP_001129080.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP26	ENST00000645722.2	c.1108-21965A>G		intron_variant			NM_001135608.3	ENSP00000495131	P1

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

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.603

Gnomad4 ASJ AF: 0.703

Gnomad4 EAS AF: 0.0850

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.706

Gnomad4 NFE AF: 0.744

Gnomad4 OTH AF: 0.599

Alfa AF: 0.682 Hom.: 9659

Bravo AF: 0.538

Asia WGS AF: 0.225 AC: 782 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.5
DANN	Benign	0.54

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

LitVar

Other links and lift over

dbSNP: rs13172733; hg19: chr5-142371680;