NM_001114753.3:c.1060C>T
Variant summary
Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001114753.3(ENG):c.1060C>T(p.Leu354Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.0149 in 1,614,118 control chromosomes in the GnomAD database, including 480 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_001114753.3 synonymous
Scores
Clinical Significance
Conservation
Publications
- telangiectasia, hereditary hemorrhagic, type 1Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, ClinGen
- hereditary hemorrhagic telangiectasiaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- juvenile polyposis syndromeInheritance: AD Classification: LIMITED Submitted by: ClinGen
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ACMG classification
Our verdict: Benign. The variant received -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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ENG | NM_001114753.3 | c.1060C>T | p.Leu354Leu | synonymous_variant | Exon 8 of 15 | ENST00000373203.9 | NP_001108225.1 | |
ENG | NM_000118.4 | c.1060C>T | p.Leu354Leu | synonymous_variant | Exon 8 of 14 | NP_000109.1 | ||
ENG | NM_001278138.2 | c.514C>T | p.Leu172Leu | synonymous_variant | Exon 8 of 15 | NP_001265067.1 | ||
ENG | NM_001406715.1 | c.1060C>T | p.Leu354Leu | synonymous_variant | Exon 8 of 8 | NP_001393644.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0334 AC: 5084AN: 152110Hom.: 180 Cov.: 30 show subpopulations
GnomAD2 exomes AF: 0.0161 AC: 4056AN: 251414 AF XY: 0.0144 show subpopulations
GnomAD4 exome AF: 0.0129 AC: 18907AN: 1461890Hom.: 299 Cov.: 33 AF XY: 0.0124 AC XY: 8993AN XY: 727246 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0334 AC: 5092AN: 152228Hom.: 181 Cov.: 30 AF XY: 0.0333 AC XY: 2478AN XY: 74452 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
not specified Benign:6
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This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
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Leu354Leu in exon 8 of ENG: This variant is not expected to have clinical signif icance because it does not alter an amino acid residue and is not located within the splice consensus sequence. It has been identified in 9.7% (427/4406) of Afr ican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs36092484). -
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Telangiectasia, hereditary hemorrhagic, type 1 Benign:2
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not provided Benign:1
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Hereditary hemorrhagic telangiectasia Benign:1
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Cardiovascular phenotype Benign:1
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at