rs27779

Variant names:

• chr5-142879518-C-A
• rs27779
• NM_001135608.3:c.384+73C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-142879518-C-A
• chr5-142879518-C-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015071.6(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_015071.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.813
• Publications: 6 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015071.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP26	NM_001135608.3	MANE Select	c.384+73C>A		intron	N/A	NP_001129080.1
	ARHGAP26	NM_015071.6		c.384+73C>A		intron	N/A	NP_055886.1
	ARHGAP26	NM_001349547.2		c.276+73C>A		intron	N/A	NP_001336476.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP26	ENST00000645722.2	MANE Select	c.384+73C>A		intron	N/A	ENSP00000495131.1
	ARHGAP26	ENST00000274498.9	TSL:1	c.384+73C>A		intron	N/A	ENSP00000274498.4
	ARHGAP26	ENST00000642734.1		c.276+73C>A		intron	N/A	ENSP00000495827.1

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

African (AFR) AF: 0.702 AC: 18359 AN: 26158

American (AMR) AF: 0.489 AC: 13035 AN: 26630

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 5914 AN: 19794

East Asian (EAS) AF: 0.803 AC: 29294 AN: 36494

South Asian (SAS) AF: 0.548 AC: 37157 AN: 67836

European-Finnish (FIN) AF: 0.275 AC: 13737 AN: 49912

Middle Eastern (MID) AF: 0.421 AC: 2132 AN: 5062

European-Non Finnish (NFE) AF: 0.263 AC: 241992 AN: 918962

Other (OTH) AF: 0.361 AC: 18334 AN: 50782

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

African (AFR) AF: 0.684 AC: 28361 AN: 41452

American (AMR) AF: 0.421 AC: 6429 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 1080 AN: 3464

East Asian (EAS) AF: 0.819 AC: 4240 AN: 5174

South Asian (SAS) AF: 0.572 AC: 2755 AN: 4820

European-Finnish (FIN) AF: 0.281 AC: 2966 AN: 10550

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.261 AC: 17766 AN: 67984

Other (OTH) AF: 0.399 AC: 843 AN: 2112

Alfa AF: 0.285 Hom.: 4192

Bravo AF: 0.451

Asia WGS AF: 0.688 AC: 2390 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.24
DANN	Benign	0.77
PhyloP100		-0.81
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: rs27779; hg19: chr5-142259083; COSMIC: COSV50825780;