chr5-143062229-T-C

Position:

• chr5-143062229-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.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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP26	NM_001135608.3	c.1538+4482T>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.1538+4482T>C		intron_variant			NM_001135608.3	ENSP00000495131.1

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

Gnomad4 AFR AF: 0.793

Gnomad4 AMR AF: 0.632

Gnomad4 ASJ AF: 0.709

Gnomad4 EAS AF: 0.717

Gnomad4 SAS AF: 0.509

Gnomad4 FIN AF: 0.728

Gnomad4 NFE AF: 0.729

Gnomad4 OTH AF: 0.717

Alfa AF: 0.715 Hom.: 78399

Bravo AF: 0.725

Asia WGS AF: 0.600 AC: 2088 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.17
DANN	Benign	0.49

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: rs3776331; hg19: chr5-142441794;