chr5-143104851-T-C

Variant names:

• chr5-143104851-T-C
• rs2398611
• NM_001135608.3:c.1539-16137T>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.1539-16137T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.778 in 152,204 control chromosomes in the GnomAD database, including 49,249 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 0.78 (49249 hom., cov: 32)
• Consequence: ARHGAP26 NM_001135608.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.331
• Publications: 1 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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.912 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP26	NM_001135608.3	c.1539-16137T>C		intron_variant	Intron 17 of 22	ENST00000645722.2	NP_001129080.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP26	ENST00000645722.2	c.1539-16137T>C		intron_variant	Intron 17 of 22		NM_001135608.3	ENSP00000495131.1

Frequencies

GnomAD3 genomes AF: 0.779 AC: 118436 AN: 152086 Hom.: 49249 Cov.: 32

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.912

Gnomad AMR AF: 0.880

Gnomad ASJ AF: 0.888

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.968

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.918

Gnomad OTH AF: 0.804

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

GnomAD4 genome AF: 0.778 AC: 118467 AN: 152204 Hom.: 49249 Cov.: 32 AF XY: 0.782 AC XY: 58167 AN XY: 74386

African (AFR) AF: 0.464 AC: 19239 AN: 41482

American (AMR) AF: 0.880 AC: 13462 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.888 AC: 3083 AN: 3470

East Asian (EAS) AF: 0.707 AC: 3660 AN: 5176

South Asian (SAS) AF: 0.728 AC: 3509 AN: 4818

European-Finnish (FIN) AF: 0.968 AC: 10277 AN: 10616

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.918 AC: 62464 AN: 68020

Other (OTH) AF: 0.800 AC: 1691 AN: 2114

Alfa AF: 0.872 Hom.: 29615

Bravo AF: 0.759

Asia WGS AF: 0.693 AC: 2414 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.1
DANN	Benign	0.73
PhyloP100		0.33
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: rs2398611; hg19: chr5-142484416;