rs153170

Positions:

• chr5-142897686-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001135608.3(ARHGAP26):​c.597+3338G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 152,124 control chromosomes in the GnomAD database, including 20,138 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 0.47 (20138 hom., cov: 33)
• Consequence: ARHGAP26 NM_001135608.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.450

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP26	NM_001135608.3	c.597+3338G>A		intron_variant		ENST00000645722.2	NP_001129080.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP26	ENST00000645722.2	c.597+3338G>A		intron_variant			NM_001135608.3	ENSP00000495131	P1
ARHGAP26	ENST00000274498.9	c.597+3338G>A		intron_variant		1		ENSP00000274498
ARHGAP26	ENST00000475287.2	c.369+3338G>A		intron_variant		5		ENSP00000494415
ARHGAP26	ENST00000642734.1	c.489+3338G>A		intron_variant				ENSP00000495827

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70963 AN: 152006 Hom.: 20085 Cov.: 33

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.905

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.432

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

GnomAD4 genome AF: 0.467 AC: 71085 AN: 152124 Hom.: 20138 Cov.: 33 AF XY: 0.472 AC XY: 35072 AN XY: 74372

Gnomad4 AFR AF: 0.740

Gnomad4 AMR AF: 0.444

Gnomad4 ASJ AF: 0.335

Gnomad4 EAS AF: 0.906

Gnomad4 SAS AF: 0.648

Gnomad4 FIN AF: 0.313

Gnomad4 NFE AF: 0.294

Gnomad4 OTH AF: 0.436

Alfa AF: 0.354 Hom.: 4963

Bravo AF: 0.490

Asia WGS AF: 0.772 AC: 2683 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.28
DANN	Benign	0.75

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: rs153170; hg19: chr5-142277251;