Variant 9-27109166-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_001290077.1(TEK):c.-425A>G variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.00179 in 464,372 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0031 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 3 hom. )

Consequence

TEK
NM_001290077.1 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.07

Variant links:

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]

TEK links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 9-27109166-A-G is Benign according to our data. Variant chr9-27109166-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 366385.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00313 (477/152284) while in subpopulation AFR AF= 0.00857 (356/41548). AF 95% confidence interval is 0.00783. There are 1 homozygotes in gnomad4. There are 236 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 477 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TEK	NM_001290077.1 linkuse as main transcript	c.-425A>G		5_prime_UTR_variant	1/22
TEK	NM_001290078.1 linkuse as main transcript	c.-425A>G		5_prime_UTR_variant	1/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEK	ENST00000519097.5 linkuse as main transcript	c.-425A>G		5_prime_UTR_variant	1/21	2			Q02763-3
TEK	ENST00000615002.4 linkuse as main transcript	c.-425A>G		5_prime_UTR_variant	1/23	5

Frequencies

GnomAD3 genomes

AF:

0.00313

AC:

476

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00857

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00379

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000588

Gnomad OTH

AF:

0.00478

GnomAD4 exome

AF:

0.00114

AC:

356

AN:

312088

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

169

AN XY:

159022

show subpopulations

Gnomad4 AFR exome

AF:

0.00810

Gnomad4 AMR exome

AF:

0.00333

Gnomad4 ASJ exome

AF:

0.00140

Gnomad4 EAS exome

AF:

0.0000387

Gnomad4 SAS exome

AF:

0.0000869

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000773

Gnomad4 OTH exome

AF:

0.00346

GnomAD4 genome

AF:

0.00313

AC:

477

AN:

152284

Hom.:

Cov.:

AF XY:

0.00317

AC XY:

236

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00857

Gnomad4 AMR

AF:

0.00379

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000588

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00287

Hom.:

Bravo

AF:

0.00346

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Multiple cutaneous and mucosal venous malformations

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.90

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over