rs7527092

Variant names:

• chr1-43301467-G-A
• rs7527092
• NM_005424.5:c.58+338G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

The NM_005424.5(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 NM_005424.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.612
• Publications: 10 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: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TIE1	NM_005424.5	c.58+338G>A		intron_variant	Intron 1 of 22	ENST00000372476.8	NP_005415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIE1	ENST00000372476.8	c.58+338G>A		intron_variant	Intron 1 of 22	1	NM_005424.5	ENSP00000361554.3
TIE1	ENST00000538015.2	n.58+338G>A		intron_variant	Intron 1 of 7	1
TIE1	ENST00000714825.1	n.58+338G>A		intron_variant	Intron 1 of 22			ENSP00000520026.1

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

African (AFR) AF: 0.480 AC: 19464 AN: 40564

American (AMR) AF: 0.483 AC: 7304 AN: 15116

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 1432 AN: 3462

East Asian (EAS) AF: 0.721 AC: 3685 AN: 5110

South Asian (SAS) AF: 0.703 AC: 3350 AN: 4762

European-Finnish (FIN) AF: 0.508 AC: 5042 AN: 9928

Middle Eastern (MID) AF: 0.432 AC: 126 AN: 292

European-Non Finnish (NFE) AF: 0.491 AC: 33173 AN: 67562

Other (OTH) AF: 0.466 AC: 969 AN: 2078

Alfa AF: 0.486 Hom.: 64041

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
PhyloP100		-0.61
PromoterAI		-0.014	Neutral
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: rs7527092; hg19: chr1-43767138;