7-74053320-CTGTGTGTGTGTGTGTGTGTGTG-CTGTGTGTGTGTGTGTGTGTG

Position:

• chr7-74053320-CTGTGTGTGTGTGTGTGTGTGTG-CTGTGTGTGTGTGTGTGTGTG

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+50del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0507 in 1,549,400 control chromosomes in the GnomAD database, including 228 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.047 (221 hom., cov: 0)
  • Exomes 𝑓: 0.051 (7 hom.)
• Consequence: ELN NM_000501.4 intron
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2 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-CTG-C is Benign according to our data. Variant chr7-74053320-CTG-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 360646.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Benign=2}. Variant chr7-74053320-CTG-C is described in Lovd as [Benign]. Variant chr7-74053320-CTG-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0859 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0472 AC: 6789 AN: 143986 Hom.: 220 Cov.: 0

Gnomad AFR AF: 0.0881

Gnomad AMI AF: 0.0180

Gnomad AMR AF: 0.0412

Gnomad ASJ AF: 0.0304

Gnomad EAS AF: 0.0553

Gnomad SAS AF: 0.0509

Gnomad FIN AF: 0.0424

Gnomad MID AF: 0.0263

Gnomad NFE AF: 0.0256

Gnomad OTH AF: 0.0457

GnomAD4 exome AF: 0.0510 AC: 71727 AN: 1405312 Hom.: 7 AF XY: 0.0513 AC XY: 35702 AN XY: 696486

Gnomad4 AFR exome AF: 0.101

Gnomad4 AMR exome AF: 0.0498

Gnomad4 ASJ exome AF: 0.0423

Gnomad4 EAS exome AF: 0.0930

Gnomad4 SAS exome AF: 0.0644

Gnomad4 FIN exome AF: 0.0625

Gnomad4 NFE exome AF: 0.0466

Gnomad4 OTH exome AF: 0.0556

GnomAD4 genome AF: 0.0472 AC: 6805 AN: 144088 Hom.: 221 Cov.: 0 AF XY: 0.0485 AC XY: 3390 AN XY: 69870

Gnomad4 AFR AF: 0.0883

Gnomad4 AMR AF: 0.0411

Gnomad4 ASJ AF: 0.0304

Gnomad4 EAS AF: 0.0554

Gnomad4 SAS AF: 0.0503

Gnomad4 FIN AF: 0.0424

Gnomad4 NFE AF: 0.0256

Gnomad4 OTH AF: 0.0467

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2 Benign:2

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Supravalvar aortic stenosis Uncertain:1 Benign: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

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 18, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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;