rs27779

chr5-142879518-C-Achr5-142879518-C-G

Variant summary

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

The NM_001135608.3(ARHGAP26):c.384+73C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 1,353,670 control chromosomes in the GnomAD database, including 87,416 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 0.43 (16907 hom., cov: 32)
  • Exomes 𝑓: 0.32 (70509 hom.)
• Consequence: ARHGAP26 NM_001135608.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.813

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP26	NM_001135608.3	c.384+73C>A		intron_variant		ENST00000645722.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP26	ENST00000645722.2	c.384+73C>A		intron_variant			NM_001135608.3	P1

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64679 AN: 151922 Hom.: 16861 Cov.: 32

Gnomad AFR AF: 0.684

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.819

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.399

GnomAD4 exome AF: 0.316 AC: 379954 AN: 1201630 Hom.: 70509 AF XY: 0.321 AC XY: 192255 AN XY: 599038

Gnomad4 AFR exome AF: 0.702

Gnomad4 AMR exome AF: 0.489

Gnomad4 ASJ exome AF: 0.299

Gnomad4 EAS exome AF: 0.803

Gnomad4 SAS exome AF: 0.548

Gnomad4 FIN exome AF: 0.275

Gnomad4 NFE exome AF: 0.263

Gnomad4 OTH exome AF: 0.361

GnomAD4 genome AF: 0.426 AC: 64789 AN: 152040 Hom.: 16907 Cov.: 32 AF XY: 0.431 AC XY: 32020 AN XY: 74298

Gnomad4 AFR AF: 0.684

Gnomad4 AMR AF: 0.421

Gnomad4 ASJ AF: 0.312

Gnomad4 EAS AF: 0.819

Gnomad4 SAS AF: 0.572

Gnomad4 FIN AF: 0.281

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.399

Alfa AF: 0.281 Hom.: 3680

Bravo AF: 0.451

Asia WGS AF: 0.688 AC: 2390 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.24
Dann	Benign	0.77

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: rs27779; hg19: chr5-142259083; COSMIC: COSV50825780;