Genetic Variant TIE1:c.3107+568G>C (chr1-43320097-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005424.5(TIE1):c.3107+568G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.892 in 158,244 control chromosomes in the GnomAD database, including 63,306 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 0.89 ( 60672 hom., cov: 32)

Exomes 𝑓: 0.93 ( 2634 hom. )

Consequence

TIE1
NM_005424.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.30

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

lymphatic malformation 11
Inheritance: AD, Unknown Classification: STRONG, LIMITED Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)

TIE1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005424.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIE1	NM_005424.5	MANE Select	c.3107+568G>C		intron	N/A	NP_005415.1	P35590-1
	TIE1	NM_001253357.2		c.2972+568G>C		intron	N/A	NP_001240286.1	B4DTW8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TIE1	ENST00000372476.8	TSL:1 MANE Select	c.3107+568G>C	intron	N/A	ENSP00000361554.3	P35590-1
TIE1	ENST00000964802.1		c.2810+568G>C	intron	N/A	ENSP00000634861.1
TIE1	ENST00000964803.1		c.2549+568G>C	intron	N/A	ENSP00000634862.1

Frequencies

GnomAD3 genomes

AF:

0.890

AC:

135379

AN:

152074

Hom.:

60617

Cov.:

show subpopulations

Gnomad AFR

AF:

0.796

Gnomad AMI

AF:

0.856

Gnomad AMR

AF:

0.921

Gnomad ASJ

AF:

0.891

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.958

Gnomad FIN

AF:

0.939

Gnomad MID

AF:

0.864

Gnomad NFE

AF:

0.920

Gnomad OTH

AF:

0.894

GnomAD4 exome

AF:

0.931

AC:

5634

AN:

6052

Hom.:

2634

Cov.:

AF XY:

0.934

AC XY:

3109

AN XY:

3330

show subpopulations

African (AFR)

AF:

0.846

AC:

AN:

American (AMR)

AF:

0.940

AC:

1303

AN:

1386

Ashkenazi Jewish (ASJ)

AF:

0.947

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

172

AN:

172

South Asian (SAS)

AF:

0.964

AC:

507

AN:

526

European-Finnish (FIN)

AF:

0.970

AC:

AN:

Middle Eastern (MID)

AF:

0.944

AC:

AN:

European-Non Finnish (NFE)

AF:

0.920

AC:

3233

AN:

3514

Other (OTH)

AF:

0.929

AC:

236

AN:

254

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

156

208

260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.890

AC:

135494

AN:

152192

Hom.:

60672

Cov.:

AF XY:

0.895

AC XY:

66590

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.797

AC:

33072

AN:

41506

American (AMR)

AF:

0.921

AC:

14083

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.891

AC:

3093

AN:

3472

East Asian (EAS)

AF:

0.999

AC:

5167

AN:

5170

South Asian (SAS)

AF:

0.958

AC:

4624

AN:

4828

European-Finnish (FIN)

AF:

0.939

AC:

9953

AN:

10598

Middle Eastern (MID)

AF:

0.871

AC:

256

AN:

294

European-Non Finnish (NFE)

AF:

0.920

AC:

62581

AN:

68016

Other (OTH)

AF:

0.895

AC:

1886

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

730

1460

2191

2921

3651

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

902

1804

2706

3608

4510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.901

Hom.:

3109

Bravo

AF:

0.882

Asia WGS

AF:

0.958

AC:

3331

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

(source)

DANN

Benign

0.73

PhyloP100

1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over