rs7527092

Positions:

• chr1-43301467-G-A
• chr1-43301467-G-T

Variant summary

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

The ENST00000372476.8(TIE1):​c.58+338G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 149,782 control chromosomes in the GnomAD database, including 18,990 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 0.50 (18990 hom., cov: 27)
• Consequence: TIE1 ENST00000372476.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.612

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TIE1	NM_005424.5	c.58+338G>A		intron_variant		ENST00000372476.8	NP_005415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TIE1	ENST00000372476.8	c.58+338G>A		intron_variant		1	NM_005424.5	ENSP00000361554	P1
TIE1	ENST00000538015.1	c.58+338G>A		intron_variant		1		ENSP00000440063

Frequencies

GnomAD3 genomes AF: 0.500 AC: 74892 AN: 149672 Hom.: 18977 Cov.: 27

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.483

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.721

Gnomad SAS AF: 0.705

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.464

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.500 AC: 74947 AN: 149782 Hom.: 18990 Cov.: 27 AF XY: 0.507 AC XY: 36999 AN XY: 72988

Gnomad4 AFR AF: 0.480

Gnomad4 AMR AF: 0.483

Gnomad4 ASJ AF: 0.414

Gnomad4 EAS AF: 0.721

Gnomad4 SAS AF: 0.703

Gnomad4 FIN AF: 0.508

Gnomad4 NFE AF: 0.491

Gnomad4 OTH AF: 0.466

Alfa AF: 0.485 Hom.: 28475

Bravo AF: 0.492

Asia WGS AF: 0.682 AC: 2368 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.97
DANN	Benign	0.37

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: rs7527092; hg19: chr1-43767138;