chr7-74053320-C-CTGTG
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2
The NM_000501.4(ELN):c.1096+47_1096+50dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.030 ( 73 hom., cov: 0)
Exomes 𝑓: 0.021 ( 1 hom. )
Failed GnomAD Quality Control
Consequence
ELN
NM_000501.4 intron
NM_000501.4 intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.780
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 Benign. Variant got -9 ACMG points.
BP6
Variant 7-74053320-C-CTGTG is Benign according to our data. Variant chr7-74053320-C-CTGTG is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 360644.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=2}.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0298 (4300/144206) while in subpopulation SAS AF= 0.0498 (218/4374). AF 95% confidence interval is 0.0444. There are 73 homozygotes in gnomad4. There are 2139 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
BS2
High AC in GnomAd4 at 4300 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ELN | NM_000501.4 | c.1096+47_1096+50dup | intron_variant | ENST00000252034.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ELN | ENST00000252034.12 | c.1096+47_1096+50dup | intron_variant | 1 | NM_000501.4 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0298 AC: 4292AN: 144102Hom.: 72 Cov.: 0
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0209 AC: 29293AN: 1401404Hom.: 1 Cov.: 0 AF XY: 0.0215 AC XY: 14915AN XY: 694842
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Data not reliable, filtered out with message: AS_VQSR
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GnomAD4 genome AF: 0.0298 AC: 4300AN: 144206Hom.: 73 Cov.: 0 AF XY: 0.0306 AC XY: 2139AN XY: 69924
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Supravalvar aortic stenosis Uncertain:1Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Cutis laxa, autosomal dominant Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at