1-43320097-G-C

Position:

• chr1-43320097-G-C

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TIE1	NM_005424.5	c.3107+568G>C		intron_variant		ENST00000372476.8	NP_005415.1
TIE1	NM_001253357.2	c.2972+568G>C		intron_variant			NP_001240286.1
TIE1	XM_005271163.3	c.2978+568G>C		intron_variant			XP_005271220.1
TIE1	XM_047429343.1	c.3036+749G>C		intron_variant			XP_047285299.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TIE1	ENST00000372476.8	c.3107+568G>C		intron_variant		1	NM_005424.5	ENSP00000361554	P1
TIE1	ENST00000473014.1	n.2304G>C		non_coding_transcript_exon_variant	4/4	2
TIE1	ENST00000492874.1	n.291G>C		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.890 AC: 135379 AN: 152074 Hom.: 60617 Cov.: 32

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.: 0 AF XY: 0.934 AC XY: 3109 AN XY: 3330

Gnomad4 AFR exome AF: 0.846

Gnomad4 AMR exome AF: 0.940

Gnomad4 ASJ exome AF: 0.947

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.964

Gnomad4 FIN exome AF: 0.970

Gnomad4 NFE exome AF: 0.920

Gnomad4 OTH exome AF: 0.929

GnomAD4 genome AF: 0.890 AC: 135494 AN: 152192 Hom.: 60672 Cov.: 32 AF XY: 0.895 AC XY: 66590 AN XY: 74410

Gnomad4 AFR AF: 0.797

Gnomad4 AMR AF: 0.921

Gnomad4 ASJ AF: 0.891

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.958

Gnomad4 FIN AF: 0.939

Gnomad4 NFE AF: 0.920

Gnomad4 OTH AF: 0.895

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	13
DANN	Benign	0.73

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: rs1098182; hg19: chr1-43785768;