NM_001135608.3:c.1538+4482T>C

Variant names:

• chr5-143062229-T-C
• rs3776331
• NM_001135608.3:c.1538+4482T>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.1538+4482T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.729 in 152,094 control chromosomes in the GnomAD database, including 40,797 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 0.73 (40797 hom., cov: 32)
• Consequence: ARHGAP26 NM_001135608.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.31
• Publications: 15 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135608.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP26	NM_001135608.3	MANE Select	c.1538+4482T>C		intron	N/A	NP_001129080.1
	ARHGAP26	NM_015071.6		c.1538+4482T>C		intron	N/A	NP_055886.1
	ARHGAP26	NM_001349547.2		c.1430+4482T>C		intron	N/A	NP_001336476.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP26	ENST00000645722.2	MANE Select	c.1538+4482T>C		intron	N/A	ENSP00000495131.1
	ARHGAP26	ENST00000274498.9	TSL:1	c.1538+4482T>C		intron	N/A	ENSP00000274498.4
	ARHGAP26	ENST00000418236.5	TSL:1	c.251+4482T>C		intron	N/A	ENSP00000416889.1

Frequencies

GnomAD3 genomes AF: 0.729 AC: 110761 AN: 151976 Hom.: 40754 Cov.: 32

Gnomad AFR AF: 0.792

Gnomad AMI AF: 0.827

Gnomad AMR AF: 0.633

Gnomad ASJ AF: 0.709

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.729

Gnomad OTH AF: 0.718

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

GnomAD4 genome AF: 0.729 AC: 110862 AN: 152094 Hom.: 40797 Cov.: 32 AF XY: 0.722 AC XY: 53682 AN XY: 74336

African (AFR) AF: 0.793 AC: 32870 AN: 41474

American (AMR) AF: 0.632 AC: 9653 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.709 AC: 2461 AN: 3470

East Asian (EAS) AF: 0.717 AC: 3709 AN: 5172

South Asian (SAS) AF: 0.509 AC: 2455 AN: 4822

European-Finnish (FIN) AF: 0.728 AC: 7696 AN: 10576

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.729 AC: 49564 AN: 67996

Other (OTH) AF: 0.717 AC: 1513 AN: 2110

Alfa AF: 0.717 Hom.: 116474

Bravo AF: 0.725

Asia WGS AF: 0.600 AC: 2088 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.17
DANN	Benign	0.49
PhyloP100		-2.3
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: rs3776331; hg19: chr5-142441794;