rs782185396
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP3BS2
The NM_000501.4(ELN):βc.771_773delβ(p.Ala260del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.0000041 in 1,461,802 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β ).
Frequency
Genomes: π 0.0 ( 0 hom., cov: 33)
Exomes π: 0.0000041 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
ELN
NM_000501.4 inframe_deletion
NM_000501.4 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.90
Genes affected
ELN (HGNC:3327): (elastin) This gene encodes a protein that is one of the two components of elastic fibers. Elastic fibers comprise part of the extracellular matrix and confer elasticity to organs and tissues including the heart, skin, lungs, ligaments, and blood vessels. The encoded protein is rich in hydrophobic amino acids such as glycine and proline, which form mobile hydrophobic regions bounded by crosslinks between lysine residues. Degradation products of the encoded protein, known as elastin-derived peptides or elastokines, bind the elastin receptor complex and other receptors and stimulate migration and proliferation of monocytes and skin fibroblasts. Elastokines can also contribute to cancer progression. Deletions and mutations in this gene are associated with supravalvular aortic stenosis (SVAS) and autosomal dominant cutis laxa. [provided by RefSeq, Aug 2017]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP3
?
Nonframeshift variant in repetitive region in NM_000501.4
BS2
?
High AC in GnomAdExome4 at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ELN | NM_000501.4 | c.771_773del | p.Ala260del | inframe_deletion | 15/33 | ENST00000252034.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ELN | ENST00000252034.12 | c.771_773del | p.Ala260del | inframe_deletion | 15/33 | 1 | NM_000501.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 0AN: 152070Hom.: 0 Cov.: 33 FAILED QC
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GnomAD3 exomes AF: 0.0000120 AC: 3AN: 249006Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 134798
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GnomAD4 genome ? Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 152070Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74284
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Supravalvar aortic stenosis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 01, 2023 | This variant, c.771_773del, results in the deletion of 1 amino acid(s) of the ELN protein (p.Ala260del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs782185396, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with ELN-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. - |
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at