7-74053320-CTGTGTGTGTGTGTGTGTGTGTG-CTGTGTGTGTGTGTGTGTGTGTGTGTG

Position:

• chr7-74053320-CTGTGTGTGTGTGTGTGTGTGTG-CTGTGTGTGTGTGTGTGTGTGTGTGTG

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BS1 BS2

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
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2 B:1
• 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-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: 4292 AN: 144102 Hom.: 72 Cov.: 0

Gnomad AFR AF: 0.0346

Gnomad AMI AF: 0.0158

Gnomad AMR AF: 0.0237

Gnomad ASJ AF: 0.0543

Gnomad EAS AF: 0.0363

Gnomad SAS AF: 0.0486

Gnomad FIN AF: 0.0226

Gnomad MID AF: 0.0428

Gnomad NFE AF: 0.0267

Gnomad OTH AF: 0.0223

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0209 AC: 29293 AN: 1401404 Hom.: 1 Cov.: 0 AF XY: 0.0215 AC XY: 14915 AN XY: 694842

Gnomad4 AFR exome AF: 0.0282

Gnomad4 AMR exome AF: 0.0139

Gnomad4 ASJ exome AF: 0.0370

Gnomad4 EAS exome AF: 0.0218

Gnomad4 SAS exome AF: 0.0378

Gnomad4 FIN exome AF: 0.0174

Gnomad4 NFE exome AF: 0.0194

Gnomad4 OTH exome AF: 0.0209

GnomAD4 genome AF: 0.0298 AC: 4300 AN: 144206 Hom.: 73 Cov.: 0 AF XY: 0.0306 AC XY: 2139 AN XY: 69924

Gnomad4 AFR AF: 0.0346

Gnomad4 AMR AF: 0.0235

Gnomad4 ASJ AF: 0.0543

Gnomad4 EAS AF: 0.0364

Gnomad4 SAS AF: 0.0498

Gnomad4 FIN AF: 0.0226

Gnomad4 NFE AF: 0.0267

Gnomad4 OTH AF: 0.0220

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2 Benign:1

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

- -

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;