7-74053320-CTGTGTGTGTGTGTGTGTGTGTG-CTGTGTGTGTGTGTGTGTGTGTGTG

Position:

• chr7-74053320-CTGTGTGTGTGTGTGTGTGTGTG-CTGTGTGTGTGTGTGTGTGTGTGTG

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BA1

The NM_000501.4(ELN):​c.1096+49_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 0.13 (1264 hom., cov: 0)
  • Exomes 𝑓: 0.11 (4 hom.)
• Consequence: ELN NM_000501.4 intron
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:4 B:2
• 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]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP6: Variant 7-74053320-C-CTG is Benign according to our data. Variant chr7-74053320-C-CTG is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 360643.We mark this variant Likely_benign, oryginal submissions are: {Benign=2, Uncertain_significance=4}.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELN	NM_000501.4	c.1096+49_1096+50dup		intron_variant		ENST00000252034.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELN	ENST00000252034.12	c.1096+49_1096+50dup		intron_variant		1	NM_000501.4	P4

Frequencies

GnomAD3 genomes AF: 0.134 AC: 19364 AN: 144016 Hom.: 1263 Cov.: 0

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.0945

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.197

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.146

GnomAD4 exome AF: 0.113 AC: 154927 AN: 1376902 Hom.: 4 Cov.: 0 AF XY: 0.112 AC XY: 76710 AN XY: 682936

Gnomad4 AFR exome AF: 0.0989

Gnomad4 AMR exome AF: 0.0798

Gnomad4 ASJ exome AF: 0.127

Gnomad4 EAS exome AF: 0.0588

Gnomad4 SAS exome AF: 0.103

Gnomad4 FIN exome AF: 0.0845

Gnomad4 NFE exome AF: 0.117

Gnomad4 OTH exome AF: 0.116

GnomAD4 genome AF: 0.134 AC: 19374 AN: 144118 Hom.: 1264 Cov.: 0 AF XY: 0.131 AC XY: 9130 AN XY: 69874

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.170

Gnomad4 EAS AF: 0.0939

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.144

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:4 Benign:2

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Supravalvar aortic stenosis Uncertain:2 Benign:1

Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

Cutis laxa, autosomal dominant Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 26, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10579871; hg19: chr7-73467650;