chr7-74051932-A-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_000501.4(ELN):c.898A>T(p.Thr300Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000992 in 1,613,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T300I) has been classified as Likely benign.
Frequency
Consequence
NM_000501.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ELN | NM_000501.4 | c.898A>T | p.Thr300Ser | missense_variant | 17/33 | ENST00000252034.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ELN | ENST00000252034.12 | c.898A>T | p.Thr300Ser | missense_variant | 17/33 | 1 | NM_000501.4 | P4 |
Frequencies
GnomAD3 genomes AF: 0.00000660 AC: 1AN: 151554Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 251034Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135818
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461466Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 727040
GnomAD4 genome AF: 0.00000660 AC: 1AN: 151554Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 73990
ClinVar
Submissions by phenotype
Inguinal hernia;C0042345:Varicose disease;C0151544:Gastrointestinal carcinoma;C0423798:Bruising susceptibility;C0949059:Colorectal polyposis;C1298820:Aortic root aneurysm;C1848771:Prominent superficial blood vessels;C4476551:Dilatation of the sinus of Valsalva Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Jan 01, 2017 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2020 | - - |
Supravalvar aortic stenosis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 29, 2023 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ELN protein function. ClinVar contains an entry for this variant (Variation ID: 523433). This variant has not been reported in the literature in individuals affected with ELN-related conditions. This variant is present in population databases (rs766735416, gnomAD 0.0009%). This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 300 of the ELN protein (p.Thr300Ser). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at