chr8-107251941-G-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_001146.5(ANGPT1):c.1411C>A(p.Leu471Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000731 in 1,613,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. L471L) has been classified as Likely benign.
Frequency
Consequence
NM_001146.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANGPT1 | NM_001146.5 | c.1411C>A | p.Leu471Met | missense_variant | 9/9 | ENST00000517746.6 | |
ANGPT1 | NM_001199859.3 | c.1408C>A | p.Leu470Met | missense_variant | 9/9 | ||
ANGPT1 | NM_001314051.2 | c.811C>A | p.Leu271Met | missense_variant | 8/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANGPT1 | ENST00000517746.6 | c.1411C>A | p.Leu471Met | missense_variant | 9/9 | 1 | NM_001146.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152082Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000119 AC: 30AN: 251404Hom.: 0 AF XY: 0.000125 AC XY: 17AN XY: 135868
GnomAD4 exome AF: 0.0000773 AC: 113AN: 1461690Hom.: 0 Cov.: 30 AF XY: 0.0000660 AC XY: 48AN XY: 727138
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152082Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74280
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 16, 2020 | This sequence change replaces leucine with methionine at codon 471 of the ANGPT1 protein (p.Leu471Met). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and methionine. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with ANGPT1-related conditions. This variant is present in population databases (rs199579578, ExAC 0.03%). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at