rs884843

Positions:

• chr7-74031459-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000501.4(ELN):​c.82+3190A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 151,954 control chromosomes in the GnomAD database, including 13,662 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.42 (13662 hom., cov: 32)
• Consequence: ELN NM_000501.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0230

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELN	NM_000501.4	c.82+3190A>G		intron_variant		ENST00000252034.12	NP_000492.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELN	ENST00000252034.12	c.82+3190A>G		intron_variant		1	NM_000501.4	ENSP00000252034	P4

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63657 AN: 151836 Hom.: 13635 Cov.: 32

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.442

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.419 AC: 63720 AN: 151954 Hom.: 13662 Cov.: 32 AF XY: 0.417 AC XY: 30989 AN XY: 74248

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.387

Gnomad4 ASJ AF: 0.492

Gnomad4 EAS AF: 0.354

Gnomad4 SAS AF: 0.364

Gnomad4 FIN AF: 0.445

Gnomad4 NFE AF: 0.461

Gnomad4 OTH AF: 0.449

Alfa AF: 0.449 Hom.: 9607

Bravo AF: 0.414

Asia WGS AF: 0.430 AC: 1493 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.0
DANN	Benign	0.58

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: rs884843; hg19: chr7-73445789;