rs868005

Positions:

• chr7-74030784-T-C

Variant summary

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

The NM_000501.4(ELN):​c.82+2515T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 151,966 control chromosomes in the GnomAD database, including 7,943 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 0.30 (7943 hom., cov: 31)
• Consequence: ELN NM_000501.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.320

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 = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELN	NM_000501.4	c.82+2515T>C		intron_variant		ENST00000252034.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELN	ENST00000252034.12	c.82+2515T>C		intron_variant		1	NM_000501.4	P4

Frequencies

GnomAD3 genomes AF: 0.296 AC: 45016 AN: 151848 Hom.: 7931 Cov.: 31

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.296 AC: 45038 AN: 151966 Hom.: 7943 Cov.: 31 AF XY: 0.291 AC XY: 21630 AN XY: 74266

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.464

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.347

Gnomad4 NFE AF: 0.403

Gnomad4 OTH AF: 0.349

Alfa AF: 0.358 Hom.: 2445

Bravo AF: 0.285

Asia WGS AF: 0.249 AC: 866 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	3.7
DANN	Benign	0.70

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: rs868005; hg19: chr7-73445114;