chr1-43321766-A-T

Variant names:

• chr1-43321766-A-T
• rs11210834
• NM_005424.5:c.3345+51A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005424.5(TIE1):​c.3345+51A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000729 in 1,372,508 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: TIE1 NM_005424.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.380
• Publications: 0 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: AD, Unknown Classification: STRONG, LIMITED Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005424.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIE1	NM_005424.5	MANE Select	c.3345+51A>T		intron	N/A	NP_005415.1	P35590-1
	TIE1	NM_001253357.2		c.3210+51A>T		intron	N/A	NP_001240286.1	B4DTW8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIE1	ENST00000372476.8	TSL:1 MANE Select	c.3345+51A>T		intron	N/A	ENSP00000361554.3	P35590-1
	TIE1	ENST00000964802.1		c.3048+51A>T		intron	N/A	ENSP00000634861.1
	TIE1	ENST00000964803.1		c.2787+51A>T		intron	N/A	ENSP00000634862.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.29e-7 AC: 1 AN: 1372508 Hom.: 0 Cov.: 26 AF XY: 0.00000148 AC XY: 1 AN XY: 677762

African (AFR) AF: 0.00 AC: 0 AN: 31000

American (AMR) AF: 0.00 AC: 0 AN: 35620

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24994

East Asian (EAS) AF: 0.00 AC: 0 AN: 35574

South Asian (SAS) AF: 0.0000127 AC: 1 AN: 78670

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47654

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5188

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1056860

Other (OTH) AF: 0.00 AC: 0 AN: 56948

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.1
DANN	Benign	0.62
PhyloP100		0.38

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

Other links and lift over

dbSNP: rs11210834; hg19: chr1-43787437;