chr5-143226004-C-T

Variant names:

• chr5-143226004-C-T
• rs187729
• NM_001135608.3:c.*3558C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001135608.3(ARHGAP26):​c.*3558C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 215,522 control chromosomes in the GnomAD database, including 43,566 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.63 (32403 hom., cov: 32)
  • Exomes 𝑓: 0.58 (11163 hom.)
• Consequence: ARHGAP26 NM_001135608.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.420
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 5-143226004-C-T is Benign according to our data. Variant chr5-143226004-C-T is described in ClinVar as Benign. ClinVar VariationId is 1250331.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP26	NM_001135608.3	c.*3558C>T		3_prime_UTR_variant	Exon 23 of 23	ENST00000645722.2	NP_001129080.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP26	ENST00000645722.2	c.*3558C>T		3_prime_UTR_variant	Exon 23 of 23		NM_001135608.3	ENSP00000495131.1
ARHGAP26	ENST00000274498.9	c.*3558C>T		3_prime_UTR_variant	Exon 23 of 23	1		ENSP00000274498.4
ARHGAP26	ENST00000486650.1	n.4271C>T		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes AF: 0.632 AC: 96006 AN: 151898 Hom.: 32341 Cov.: 32

Gnomad AFR AF: 0.878

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.581

Gnomad EAS AF: 0.774

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.597

GnomAD4 exome AF: 0.577 AC: 36658 AN: 63506 Hom.: 11163 Cov.: 0 AF XY: 0.572 AC XY: 16902 AN XY: 29564

African (AFR) AF: 0.864 AC: 2474 AN: 2864

American (AMR) AF: 0.562 AC: 1089 AN: 1938

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 2344 AN: 3996

East Asian (EAS) AF: 0.815 AC: 7656 AN: 9394

South Asian (SAS) AF: 0.593 AC: 337 AN: 568

European-Finnish (FIN) AF: 0.546 AC: 237 AN: 434

Middle Eastern (MID) AF: 0.663 AC: 248 AN: 374

European-Non Finnish (NFE) AF: 0.499 AC: 19352 AN: 38756

Other (OTH) AF: 0.564 AC: 2921 AN: 5182

GnomAD4 genome AF: 0.632 AC: 96125 AN: 152016 Hom.: 32403 Cov.: 32 AF XY: 0.636 AC XY: 47278 AN XY: 74298

African (AFR) AF: 0.878 AC: 36410 AN: 41468

American (AMR) AF: 0.587 AC: 8973 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.581 AC: 2016 AN: 3470

East Asian (EAS) AF: 0.774 AC: 3995 AN: 5162

South Asian (SAS) AF: 0.598 AC: 2879 AN: 4814

European-Finnish (FIN) AF: 0.577 AC: 6089 AN: 10550

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.498 AC: 33825 AN: 67958

Other (OTH) AF: 0.599 AC: 1265 AN: 2112

Alfa AF: 0.579 Hom.: 13675

Bravo AF: 0.644

Asia WGS AF: 0.705 AC: 2454 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 15, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 24886876) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.1
DANN	Benign	0.28
PhyloP100		-0.42
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: rs187729; hg19: chr5-142605569; COSMIC: COSV50826587; COSMIC: COSV50826587;