rs10515520

Variant names:

• chr5-143206727-G-A
• rs10515520
• NM_001135608.3:c.1989-471G>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.1989-471G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,120 control chromosomes in the GnomAD database, including 2,109 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 0.16 (2109 hom., cov: 33)
• Consequence: ARHGAP26 NM_001135608.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21
• 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=-0.55).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP26	NM_001135608.3	c.1989-471G>A		intron_variant	Intron 20 of 22	ENST00000645722.2	NP_001129080.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP26	ENST00000645722.2	c.1989-471G>A		intron_variant	Intron 20 of 22		NM_001135608.3	ENSP00000495131.1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25058 AN: 152000 Hom.: 2107 Cov.: 33

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.165 AC: 25085 AN: 152120 Hom.: 2109 Cov.: 33 AF XY: 0.166 AC XY: 12363 AN XY: 74332

African (AFR) AF: 0.188 AC: 7807 AN: 41492

American (AMR) AF: 0.122 AC: 1873 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 567 AN: 3468

East Asian (EAS) AF: 0.154 AC: 797 AN: 5172

South Asian (SAS) AF: 0.123 AC: 595 AN: 4826

European-Finnish (FIN) AF: 0.214 AC: 2256 AN: 10562

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10730 AN: 67994

Other (OTH) AF: 0.155 AC: 327 AN: 2108

Alfa AF: 0.164 Hom.: 739

Bravo AF: 0.162

Asia WGS AF: 0.177 AC: 615 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	9.0
DANN	Benign	0.72
PhyloP100		1.2
PromoterAI		0.27	Neutral
Mutation Taster		=99/1	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: rs10515520; hg19: chr5-142586292;