rs1467809

chr1-43308766-G-Achr1-43308766-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TIE1	NM_005424.5	c.1043-220G>A		intron_variant		ENST00000372476.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TIE1	ENST00000372476.8	c.1043-220G>A		intron_variant		1	NM_005424.5	P1
TIE1	ENST00000538015.1	c.1043-105G>A		intron_variant		1
TIE1	ENST00000480269.1	n.274-220G>A		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR exome AF: 0.796

Gnomad4 AMR exome AF: 0.679

Gnomad4 ASJ exome AF: 0.581

Gnomad4 EAS exome AF: 0.816

Gnomad4 SAS exome AF: 0.831

Gnomad4 FIN exome AF: 0.672

Gnomad4 NFE exome AF: 0.616

Gnomad4 OTH exome AF: 0.658

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

Gnomad4 AFR AF: 0.797

Gnomad4 AMR AF: 0.632

Gnomad4 ASJ AF: 0.585

Gnomad4 EAS AF: 0.845

Gnomad4 SAS AF: 0.842

Gnomad4 FIN AF: 0.659

Gnomad4 NFE AF: 0.623

Gnomad4 OTH AF: 0.640

Alfa AF: 0.633 Hom.: 62449

Bravo AF: 0.690

Asia WGS AF: 0.842 AC: 2927 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.7
Dann	Benign	0.40

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

Publications

LitVar

Other links and lift over

dbSNP: rs1467809; hg19: chr1-43774437;