9-27187424-G-T

Position:

• chr9-27187424-G-T

Variant summary

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

The NM_000459.5(TEK):​c.1327+1795G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 151,986 control chromosomes in the GnomAD database, including 15,631 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 0.45 (15631 hom., cov: 33)
• Consequence: TEK NM_000459.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.118

Genes affected

TEK (HGNC:11724): (TEK receptor tyrosine kinase) This gene encodes a receptor that belongs to the protein tyrosine kinase Tie2 family. The encoded protein possesses a unique extracellular region that contains two immunoglobulin-like domains, three epidermal growth factor (EGF)-like domains and three fibronectin type III repeats. The ligand angiopoietin-1 binds to this receptor and mediates a signaling pathway that functions in embryonic vascular development. Mutations in this gene are associated with inherited venous malformations of the skin and mucous membranes. Alternative splicing results in multiple transcript variants. Additional alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Feb 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TEK	NM_000459.5	c.1327+1795G>T		intron_variant		ENST00000380036.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEK	ENST00000380036.10	c.1327+1795G>T		intron_variant		1	NM_000459.5	P1

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67854 AN: 151866 Hom.: 15602 Cov.: 33

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.485

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.460

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

GnomAD4 genome AF: 0.447 AC: 67935 AN: 151986 Hom.: 15631 Cov.: 33 AF XY: 0.449 AC XY: 33370 AN XY: 74292

Gnomad4 AFR AF: 0.448

Gnomad4 AMR AF: 0.531

Gnomad4 ASJ AF: 0.441

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.493

Gnomad4 FIN AF: 0.485

Gnomad4 NFE AF: 0.442

Gnomad4 OTH AF: 0.460

Alfa AF: 0.450 Hom.: 20995

Bravo AF: 0.452

Asia WGS AF: 0.334 AC: 1166 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.0
DANN	Benign	0.31

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: rs581724; hg19: chr9-27187422; COSMIC: COSV66228247;