7-74053320-CTGTGTGTGTGTGTGTGTGTGTG-CTGTGTGTGTGTGTGTG

Position:

• chr7-74053320-CTGTGTGTGTGTGTGTGTGTGTG-CTGTGTGTGTGTGTGTG

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000501.4(ELN):​c.1096+45_1096+50del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 1,443,618 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0050 (3 hom., cov: 0)
  • Exomes 𝑓: 0.13 (0 hom.)
• Consequence: ELN NM_000501.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.33

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 -16 ACMG points.

• BP6: Variant 7-74053320-CTGTGTG-C is Benign according to our data. Variant chr7-74053320-CTGTGTG-C is described in ClinVar as [Benign]. Clinvar id is 360647.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74053320-CTGTGTG-C is described in Lovd as [Benign]. Variant chr7-74053320-CTGTGTG-C is described in Lovd as [Benign].
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELN	NM_000501.4	c.1096+45_1096+50del		intron_variant		ENST00000252034.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELN	ENST00000252034.12	c.1096+45_1096+50del		intron_variant		1	NM_000501.4	P4

Frequencies

GnomAD3 genomes AF: 0.00502 AC: 721 AN: 143600 Hom.: 3 Cov.: 0

Gnomad AFR AF: 0.00485

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00828

Gnomad ASJ AF: 0.00118

Gnomad EAS AF: 0.00348

Gnomad SAS AF: 0.00251

Gnomad FIN AF: 0.0124

Gnomad MID AF: 0.00667

Gnomad NFE AF: 0.00399

Gnomad OTH AF: 0.00254

GnomAD4 exome AF: 0.129 AC: 167807 AN: 1299932 Hom.: 0 AF XY: 0.131 AC XY: 84468 AN XY: 646200

Gnomad4 AFR exome AF: 0.100

Gnomad4 AMR exome AF: 0.181

Gnomad4 ASJ exome AF: 0.166

Gnomad4 EAS exome AF: 0.152

Gnomad4 SAS exome AF: 0.142

Gnomad4 FIN exome AF: 0.157

Gnomad4 NFE exome AF: 0.124

Gnomad4 OTH exome AF: 0.135

GnomAD4 genome AF: 0.00504 AC: 724 AN: 143686 Hom.: 3 Cov.: 0 AF XY: 0.00543 AC XY: 378 AN XY: 69622

Gnomad4 AFR AF: 0.00491

Gnomad4 AMR AF: 0.00828

Gnomad4 ASJ AF: 0.00118

Gnomad4 EAS AF: 0.00348

Gnomad4 SAS AF: 0.00252

Gnomad4 FIN AF: 0.0124

Gnomad4 NFE AF: 0.00399

Gnomad4 OTH AF: 0.00252

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -

Supravalvar aortic stenosis Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 24, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

Cutis laxa, autosomal dominant Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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;