Variant 1-43305342-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_005424.5(TIE1):c.483C>T(p.Asn161Asn) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000378 in 1,494,268 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0032 ( 0 hom., cov: 24)

Exomes 𝑓: 0.00021 ( 1 hom. )

Consequence

TIE1
NM_005424.5 splice_region, synonymous

Scores

Splicing: ADA: 0.003036

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.308

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 Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 1-43305342-C-T is Benign according to our data. Variant chr1-43305342-C-T is described in ClinVar as [Benign]. Clinvar id is 780767.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.308 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TIE1	NM_005424.5 linkuse as main transcript	c.483C>T	p.Asn161Asn	splice_region_variant, synonymous_variant	3/23	ENST00000372476.8	NP_005415.1	P35590-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TIE1	ENST00000372476.8 linkuse as main transcript	c.483C>T	p.Asn161Asn	splice_region_variant, synonymous_variant	3/23	1	NM_005424.5	ENSP00000361554.3	P35590-1
TIE1	ENST00000538015.1 linkuse as main transcript	c.483C>T	p.Asn161Asn	splice_region_variant, synonymous_variant	3/8	1			P35590-2
TIE1	ENST00000485125.1 linkuse as main transcript	n.556C>T		splice_region_variant, non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.00325

AC:

264

AN:

81280

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0138

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000881

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000483

Gnomad OTH

AF:

0.00326

GnomAD3 exomes

AF:

0.00142

AC:

116

AN:

81962

Hom.:

AF XY:

0.00122

AC XY:

AN XY:

41930

show subpopulations

Gnomad AFR exome

AF:

0.0206

Gnomad AMR exome

AF:

0.000652

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000244

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000463

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000213

AC:

301

AN:

1412902

Hom.:

Cov.:

AF XY:

0.000193

AC XY:

134

AN XY:

695520

show subpopulations

Gnomad4 AFR exome

AF:

0.00729

Gnomad4 AMR exome

AF:

0.000362

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000255

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000148

Gnomad4 OTH exome

AF:

0.000463

GnomAD4 genome

AF:

0.00324

AC:

264

AN:

81366

Hom.:

Cov.:

AF XY:

0.00339

AC XY:

133

AN XY:

39280

show subpopulations

Gnomad4 AFR

AF:

0.0137

Gnomad4 AMR

AF:

0.000880

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000483

Gnomad4 OTH

AF:

0.00323

Alfa

AF:

0.000356

Hom.:

Bravo

AF:

0.00206

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 14, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0030

dbscSNV1_RF

Benign

0.14

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