rs11210834

Positions:

• chr1-43321766-A-G

Variant summary

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

The NM_005424.5(TIE1):​c.3345+51A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 1,523,580 control chromosomes in the GnomAD database, including 48,187 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 0.24 (4524 hom., cov: 32)
  • Exomes 𝑓: 0.25 (43663 hom.)
• Consequence: TIE1 NM_005424.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.380

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 = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TIE1	NM_005424.5	c.3345+51A>G		intron_variant		ENST00000372476.8	NP_005415.1
TIE1	NM_001253357.2	c.3210+51A>G		intron_variant			NP_001240286.1
TIE1	XM_005271163.3	c.3216+51A>G		intron_variant			XP_005271220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TIE1	ENST00000372476.8	c.3345+51A>G		intron_variant		1	NM_005424.5	ENSP00000361554.3

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36289 AN: 151892 Hom.: 4519 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.234

GnomAD3 exomes AF: 0.269 AC: 41232 AN: 153006 Hom.: 5929 AF XY: 0.272 AC XY: 21887 AN XY: 80480

Gnomad AFR exome AF: 0.174

Gnomad AMR exome AF: 0.255

Gnomad ASJ exome AF: 0.244

Gnomad EAS exome AF: 0.441

Gnomad SAS exome AF: 0.289

Gnomad FIN exome AF: 0.311

Gnomad NFE exome AF: 0.245

Gnomad OTH exome AF: 0.243

GnomAD4 exome AF: 0.250 AC: 342227 AN: 1371570 Hom.: 43663 Cov.: 26 AF XY: 0.251 AC XY: 169982 AN XY: 677320

Gnomad4 AFR exome AF: 0.168

Gnomad4 AMR exome AF: 0.252

Gnomad4 ASJ exome AF: 0.240

Gnomad4 EAS exome AF: 0.378

Gnomad4 SAS exome AF: 0.291

Gnomad4 FIN exome AF: 0.313

Gnomad4 NFE exome AF: 0.242

Gnomad4 OTH exome AF: 0.248

GnomAD4 genome AF: 0.239 AC: 36313 AN: 152010 Hom.: 4524 Cov.: 32 AF XY: 0.242 AC XY: 18008 AN XY: 74314

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.418

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.309

Gnomad4 NFE AF: 0.250

Gnomad4 OTH AF: 0.239

Alfa AF: 0.243 Hom.: 8504

Bravo AF: 0.232

Asia WGS AF: 0.333 AC: 1158 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	4.6
DANN	Benign	0.57

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: rs11210834; hg19: chr1-43787437; COSMIC: COSV65249027; COSMIC: COSV65249027;