rs1155226

Positions:

• chr5-142790609-T-C

Variant summary

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

The NM_001135608.3(ARHGAP26):​c.154+19694T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,164 control chromosomes in the GnomAD database, including 8,496 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 0.24 (8496 hom., cov: 32)
• Consequence: ARHGAP26 NM_001135608.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.178

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP26	NM_001135608.3	c.154+19694T>C		intron_variant		ENST00000645722.2	NP_001129080.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP26	ENST00000645722.2	c.154+19694T>C		intron_variant			NM_001135608.3	ENSP00000495131	P1
ARHGAP26	ENST00000274498.9	c.154+19694T>C		intron_variant		1		ENSP00000274498
ARHGAP26	ENST00000642734.1	c.46+19234T>C		intron_variant				ENSP00000495827
ARHGAP26	ENST00000378013.2	n.134+17759T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.237 AC: 35987 AN: 152046 Hom.: 8442 Cov.: 32

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.0694

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.0683

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.0820

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.237 AC: 36101 AN: 152164 Hom.: 8496 Cov.: 32 AF XY: 0.231 AC XY: 17195 AN XY: 74408

Gnomad4 AFR AF: 0.615

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.168

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.0683

Gnomad4 NFE AF: 0.0820

Gnomad4 OTH AF: 0.200

Alfa AF: 0.118 Hom.: 2116

Bravo AF: 0.261

Asia WGS AF: 0.179 AC: 624 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.5
DANN	Benign	0.67

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: rs1155226; hg19: chr5-142170174;