rs2991990

chr1-43314198-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005424.5(TIE1):c.2409+230T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 703,858 control chromosomes in the GnomAD database, including 158,621 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 0.70 (37729 hom., cov: 32)
  • Exomes 𝑓: 0.66 (120892 hom.)
• Consequence: TIE1 NM_005424.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.251

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=-0.65).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TIE1	NM_005424.5	c.2409+230T>G		intron_variant		ENST00000372476.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TIE1	ENST00000372476.8	c.2409+230T>G		intron_variant		1	NM_005424.5	P1
TIE1	ENST00000461061.1	n.430-185T>G		intron_variant, non_coding_transcript_variant		3
TIE1	ENST00000473014.1	n.677+230T>G		intron_variant, non_coding_transcript_variant		2
TIE1	ENST00000471187.1			downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.698 AC: 106040 AN: 151992 Hom.: 37701 Cov.: 32

Gnomad AFR AF: 0.830

Gnomad AMI AF: 0.611

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.857

Gnomad SAS AF: 0.845

Gnomad FIN AF: 0.659

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.623

Gnomad OTH AF: 0.647

GnomAD4 exome AF: 0.655 AC: 361436 AN: 551748 Hom.: 120892 Cov.: 7 AF XY: 0.662 AC XY: 187899 AN XY: 283826

Gnomad4 AFR exome AF: 0.829

Gnomad4 AMR exome AF: 0.658

Gnomad4 ASJ exome AF: 0.586

Gnomad4 EAS exome AF: 0.824

Gnomad4 SAS exome AF: 0.833

Gnomad4 FIN exome AF: 0.669

Gnomad4 NFE exome AF: 0.614

Gnomad4 OTH exome AF: 0.658

GnomAD4 genome AF: 0.698 AC: 106122 AN: 152110 Hom.: 37729 Cov.: 32 AF XY: 0.701 AC XY: 52115 AN XY: 74352

Gnomad4 AFR AF: 0.830

Gnomad4 AMR AF: 0.637

Gnomad4 ASJ AF: 0.585

Gnomad4 EAS AF: 0.857

Gnomad4 SAS AF: 0.844

Gnomad4 FIN AF: 0.659

Gnomad4 NFE AF: 0.623

Gnomad4 OTH AF: 0.648

Alfa AF: 0.629 Hom.: 27498

Bravo AF: 0.700

Asia WGS AF: 0.849 AC: 2953 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
Cadd	Benign	5.5
Dann	Benign	0.75

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

Other links and lift over

dbSNP: rs2991990; hg19: chr1-43779869;