chr9-27209471-A-C

Position:

• chr9-27209471-A-C

Variant summary

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

The NM_000459.5(TEK):​c.2686+240A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0358 in 152,202 control chromosomes in the GnomAD database, including 129 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 0.036 (129 hom., cov: 32)
• Consequence: TEK NM_000459.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00900

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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEK	NM_000459.5	c.2686+240A>C		intron_variant		ENST00000380036.10	NP_000450.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEK	ENST00000380036.10	c.2686+240A>C		intron_variant		1	NM_000459.5	ENSP00000369375.4
TEK	ENST00000406359.8	c.2557+240A>C		intron_variant		2		ENSP00000383977.4
TEK	ENST00000519097.5	c.2242+240A>C		intron_variant		2		ENSP00000430686.1
TEK	ENST00000615002.4	c.*1187+240A>C		intron_variant		5		ENSP00000480251.1

Frequencies

GnomAD3 genomes AF: 0.0359 AC: 5456 AN: 152084 Hom.: 129 Cov.: 32

Gnomad AFR AF: 0.00932

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.0387

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.0505

Gnomad SAS AF: 0.0628

Gnomad FIN AF: 0.0139

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0476

Gnomad OTH AF: 0.0421

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

GnomAD4 genome AF: 0.0358 AC: 5454 AN: 152202 Hom.: 129 Cov.: 32 AF XY: 0.0352 AC XY: 2622 AN XY: 74406

Gnomad4 AFR AF: 0.00930

Gnomad4 AMR AF: 0.0386

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.0506

Gnomad4 SAS AF: 0.0622

Gnomad4 FIN AF: 0.0139

Gnomad4 NFE AF: 0.0476

Gnomad4 OTH AF: 0.0417

Alfa AF: 0.0484 Hom.: 109

Bravo AF: 0.0362

Asia WGS AF: 0.0380 AC: 132 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.0
DANN	Benign	0.45

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: rs2273720; hg19: chr9-27209469;