1-43308766-G-A

Variant names:

• chr1-43308766-G-A
• rs1467809
• NM_005424.5:c.1043-220G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005424.5(TIE1):​c.1043-220G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 662,302 control chromosomes in the GnomAD database, including 151,897 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 0.69 (36338 hom., cov: 29)
  • Exomes 𝑓: 0.67 (115559 hom.)
• Consequence: TIE1 NM_005424.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.165
• Publications: 16 publications found

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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.824 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.1043-220G>A		intron	N/A	NP_005415.1	P35590-1
	TIE1	NM_001253357.2		c.908-220G>A		intron	N/A	NP_001240286.1	B4DTW8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIE1	ENST00000372476.8	TSL:1 MANE Select	c.1043-220G>A		intron	N/A	ENSP00000361554.3	P35590-1
	TIE1	ENST00000538015.2	TSL:1	n.1043-105G>A		intron	N/A
	TIE1	ENST00000964802.1		c.1043-220G>A		intron	N/A	ENSP00000634861.1

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104152 AN: 151470 Hom.: 36315 Cov.: 29

Gnomad AFR AF: 0.798

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.845

Gnomad SAS AF: 0.843

Gnomad FIN AF: 0.659

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.623

Gnomad OTH AF: 0.639

GnomAD4 exome AF: 0.667 AC: 340404 AN: 510714 Hom.: 115559 AF XY: 0.675 AC XY: 186042 AN XY: 275798

African (AFR) AF: 0.796 AC: 11933 AN: 14996

American (AMR) AF: 0.679 AC: 22406 AN: 33022

Ashkenazi Jewish (ASJ) AF: 0.581 AC: 10449 AN: 17982

East Asian (EAS) AF: 0.816 AC: 23690 AN: 29018

South Asian (SAS) AF: 0.831 AC: 49295 AN: 59322

European-Finnish (FIN) AF: 0.672 AC: 21186 AN: 31512

Middle Eastern (MID) AF: 0.621 AC: 1428 AN: 2300

European-Non Finnish (NFE) AF: 0.616 AC: 181644 AN: 294650

Other (OTH) AF: 0.658 AC: 18373 AN: 27912

GnomAD4 genome AF: 0.688 AC: 104226 AN: 151588 Hom.: 36338 Cov.: 29 AF XY: 0.691 AC XY: 51157 AN XY: 74070

African (AFR) AF: 0.797 AC: 32885 AN: 41246

American (AMR) AF: 0.632 AC: 9655 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.585 AC: 2032 AN: 3472

East Asian (EAS) AF: 0.845 AC: 4331 AN: 5126

South Asian (SAS) AF: 0.842 AC: 4045 AN: 4806

European-Finnish (FIN) AF: 0.659 AC: 6944 AN: 10530

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.623 AC: 42252 AN: 67832

Other (OTH) AF: 0.640 AC: 1347 AN: 2104

Alfa AF: 0.641 Hom.: 133959

Bravo AF: 0.690

Asia WGS AF: 0.842 AC: 2927 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.7
DANN	Benign	0.40
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1467809; hg19: chr1-43774437;