NM_001135608.3:c.597+3338G>A

Variant names:

• chr5-142897686-G-A
• rs153170
• NM_001135608.3:c.597+3338G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-0.92).
• 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 rank	MANE	Protein	UniProt
ARHGAP26	NM_001135608.3	c.597+3338G>A		intron_variant	Intron 6 of 22	ENST00000645722.2	NP_001129080.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP26	ENST00000645722.2	c.597+3338G>A		intron_variant	Intron 6 of 22		NM_001135608.3	ENSP00000495131.1
ARHGAP26	ENST00000274498.9	c.597+3338G>A		intron_variant	Intron 6 of 22	1		ENSP00000274498.4
ARHGAP26	ENST00000642734.1	c.489+3338G>A		intron_variant	Intron 6 of 21			ENSP00000495827.1
ARHGAP26	ENST00000475287.2	c.369+3338G>A		intron_variant	Intron 4 of 8	5		ENSP00000494415.1

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

African (AFR) AF: 0.740 AC: 30735 AN: 41508

American (AMR) AF: 0.444 AC: 6781 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 1159 AN: 3464

East Asian (EAS) AF: 0.906 AC: 4686 AN: 5174

South Asian (SAS) AF: 0.648 AC: 3125 AN: 4822

European-Finnish (FIN) AF: 0.313 AC: 3310 AN: 10564

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.294 AC: 19998 AN: 67996

Other (OTH) AF: 0.436 AC: 920 AN: 2110

Alfa AF: 0.374 Hom.: 23345

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
PhyloP100		-0.45
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: rs153170; hg19: chr5-142277251;