9-27187218-C-G

Position:

• chr9-27187218-C-G

Variant summary

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

The NM_000459.5(TEK):​c.1327+1589C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.676 in 152,054 control chromosomes in the GnomAD database, including 35,116 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 0.68 (35116 hom., cov: 33)
• Consequence: TEK NM_000459.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0950

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEK	NM_000459.5	c.1327+1589C>G		intron_variant		ENST00000380036.10	NP_000450.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEK	ENST00000380036.10	c.1327+1589C>G		intron_variant		1	NM_000459.5	ENSP00000369375	P1

Frequencies

GnomAD3 genomes AF: 0.676 AC: 102735 AN: 151934 Hom.: 35080 Cov.: 33

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.744

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.702

Gnomad FIN AF: 0.675

Gnomad MID AF: 0.643

Gnomad NFE AF: 0.676

Gnomad OTH AF: 0.690

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

GnomAD4 genome AF: 0.676 AC: 102825 AN: 152054 Hom.: 35116 Cov.: 33 AF XY: 0.676 AC XY: 50272 AN XY: 74330

Gnomad4 AFR AF: 0.687

Gnomad4 AMR AF: 0.744

Gnomad4 ASJ AF: 0.659

Gnomad4 EAS AF: 0.382

Gnomad4 SAS AF: 0.702

Gnomad4 FIN AF: 0.675

Gnomad4 NFE AF: 0.676

Gnomad4 OTH AF: 0.688

Alfa AF: 0.581 Hom.: 1663

Bravo AF: 0.681

Asia WGS AF: 0.593 AC: 2064 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	11
DANN	Benign	0.69

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: rs489347; hg19: chr9-27187216; COSMIC: COSV66228244;