chr9-27118809-A-G

Position:

• chr9-27118809-A-G

Variant summary

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

The NM_000459.5(TEK):​c.52+9167A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 151,840 control chromosomes in the GnomAD database, including 12,381 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 0.40 (12381 hom., cov: 32)
• Consequence: TEK NM_000459.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.325

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEK	NM_000459.5	c.52+9167A>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.52+9167A>G		intron_variant		1	NM_000459.5	ENSP00000369375	P1

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60022 AN: 151720 Hom.: 12374 Cov.: 32

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.699

Gnomad SAS AF: 0.621

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.409

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

GnomAD4 genome AF: 0.396 AC: 60061 AN: 151840 Hom.: 12381 Cov.: 32 AF XY: 0.402 AC XY: 29846 AN XY: 74182

Gnomad4 AFR AF: 0.379

Gnomad4 AMR AF: 0.320

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.698

Gnomad4 SAS AF: 0.621

Gnomad4 FIN AF: 0.417

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.413

Alfa AF: 0.388 Hom.: 23970

Bravo AF: 0.383

Asia WGS AF: 0.618 AC: 2152 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.7
DANN	Benign	0.60

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: rs621786; hg19: chr9-27118807; COSMIC: COSV66233047;