Variant rs1199039 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_005424.5(TIE1):c.2973A>G(p.Leu991Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 1,613,214 control chromosomes in the GnomAD database, including 107,921 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

Frequency

Genomes: 𝑓 0.31 ( 8031 hom., cov: 29)

Exomes 𝑓: 0.36 ( 99890 hom. )

Consequence

TIE1
NM_005424.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.19

Variant links:

Genes affected

TIE1 (HGNC:11809): (tyrosine kinase with immunoglobulin like and EGF like domains 1) This gene encodes a member of the tyrosine protein kinase family. The encoded protein plays a critical role in angiogenesis and blood vessel stability by inhibiting angiopoietin 1 signaling through the endothelial receptor tyrosine kinase Tie2. Ectodomain cleavage of the encoded protein relieves inhibition of Tie2 and is mediated by multiple factors including vascular endothelial growth factor. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

TIE1 links:

TIE1 (HGNC:):

TIE1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 1-43319285-A-G is Benign according to our data. Variant chr1-43319285-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.19 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TIE1	NM_005424.5 linkuse as main transcript	c.2973A>G	p.Leu991Leu	synonymous_variant	18/23	ENST00000372476.8	NP_005415.1	P35590-1
TIE1	NM_001253357.2 linkuse as main transcript	c.2838A>G	p.Leu946Leu	synonymous_variant	18/23		NP_001240286.1	B4DTW8
TIE1	XM_005271163.3 linkuse as main transcript	c.2844A>G	p.Leu948Leu	synonymous_variant	17/22		XP_005271220.1
TIE1	XM_047429343.1 linkuse as main transcript	c.2973A>G	p.Leu991Leu	synonymous_variant	18/20		XP_047285299.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TIE1	ENST00000372476.8 linkuse as main transcript	c.2973A>G	p.Leu991Leu	synonymous_variant	18/23	1	NM_005424.5	ENSP00000361554.3	P35590-1
TIE1	ENST00000473014.1 linkuse as main transcript	n.1602A>G		non_coding_transcript_exon_variant	3/4	2
TIE1	ENST00000492599.1 linkuse as main transcript	n.194A>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.314

AC:

47630

AN:

151596

Hom.:

8026

Cov.:

show subpopulations

Gnomad AFR

AF:

0.203

Gnomad AMI

AF:

0.395

Gnomad AMR

AF:

0.371

Gnomad ASJ

AF:

0.416

Gnomad EAS

AF:

0.150

Gnomad SAS

AF:

0.162

Gnomad FIN

AF:

0.342

Gnomad MID

AF:

0.399

Gnomad NFE

AF:

0.380

Gnomad OTH

AF:

0.363

GnomAD3 exomes

AF:

0.316

AC:

79516

AN:

251444

Hom.:

13775

AF XY:

0.315

AC XY:

42812

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.195

Gnomad AMR exome

AF:

0.311

Gnomad ASJ exome

AF:

0.426

Gnomad EAS exome

AF:

0.146

Gnomad SAS exome

AF:

0.174

Gnomad FIN exome

AF:

0.340

Gnomad NFE exome

AF:

0.385

Gnomad OTH exome

AF:

0.350

GnomAD4 exome

AF:

0.363

AC:

530367

AN:

1461500

Hom.:

99890

Cov.:

AF XY:

0.358

AC XY:

260543

AN XY:

727096

show subpopulations

Gnomad4 AFR exome

AF:

0.205

Gnomad4 AMR exome

AF:

0.320

Gnomad4 ASJ exome

AF:

0.421

Gnomad4 EAS exome

AF:

0.180

Gnomad4 SAS exome

AF:

0.179

Gnomad4 FIN exome

AF:

0.331

Gnomad4 NFE exome

AF:

0.391

Gnomad4 OTH exome

AF:

0.350

GnomAD4 genome

AF:

0.314

AC:

47676

AN:

151714

Hom.:

8031

Cov.:

AF XY:

0.311

AC XY:

23025

AN XY:

74152

show subpopulations

Gnomad4 AFR

AF:

0.203

Gnomad4 AMR

AF:

0.371

Gnomad4 ASJ

AF:

0.416

Gnomad4 EAS

AF:

0.150

Gnomad4 SAS

AF:

0.164

Gnomad4 FIN

AF:

0.342

Gnomad4 NFE

AF:

0.380

Gnomad4 OTH

AF:

0.361

Alfa

AF:

0.369

Hom.:

14033

Bravo

AF:

0.313

Asia WGS

AF:

0.159

AC:

553

AN:

3478

EpiCase

AF:

0.390

EpiControl

AF:

0.392

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.66

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over