8-107251872-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_001146.5(ANGPT1):c.1480C>T(p.Arg494Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,566 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
ANGPT1
NM_001146.5 stop_gained
NM_001146.5 stop_gained
Scores
5
1
1
Clinical Significance
Conservation
PhyloP100: 8.09
Genes affected
ANGPT1 (HGNC:484): (angiopoietin 1) This gene encodes a secreted glycoprotein that belongs to the angiopoietin family. Members of this family play important roles in vascular development and angiogenesis. All angiopoietins bind with similar affinity to an endothelial cell-specific tyrosine-protein kinase receptor. The protein encoded by this gene is a secreted glycoprotein that activates the receptor by inducing its tyrosine phosphorylation. It plays a critical role in mediating reciprocal interactions between the endothelium and surrounding matrix and mesenchyme and inhibits endothelial permeability. The protein also contributes to blood vessel maturation and stability, and may be involved in early development of the heart. Mutations in this gene are associated with hereditary angioedema. [provided by RefSeq, Aug 2020]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Stoplost variant in NM_001146.5 Downstream stopcodon found after 11 codons.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANGPT1 | NM_001146.5 | c.1480C>T | p.Arg494Ter | stop_gained | 9/9 | ENST00000517746.6 | |
ANGPT1 | NM_001199859.3 | c.1477C>T | p.Arg493Ter | stop_gained | 9/9 | ||
ANGPT1 | NM_001314051.2 | c.880C>T | p.Arg294Ter | stop_gained | 8/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANGPT1 | ENST00000517746.6 | c.1480C>T | p.Arg494Ter | stop_gained | 9/9 | 1 | NM_001146.5 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461566Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 727076
GnomAD4 exome
AF:
AC:
1
AN:
1461566
Hom.:
Cov.:
30
AF XY:
AC XY:
1
AN XY:
727076
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
Alfa
AF:
Hom.:
ESP6500AA
AF:
AC:
0
ESP6500EA
AF:
AC:
1
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, no assertion criteria provided | literature only | OMIM | Nov 13, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
D;D;D;D
Vest4
GERP RS
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at