rs2239691

Positions:

• chr7-74054839-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000501.4(ELN):​c.1150+70C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 1,563,958 control chromosomes in the GnomAD database, including 110,961 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7956 hom., cov: 32)
  • Exomes 𝑓: 0.37 (103005 hom.)
• Consequence: ELN NM_000501.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.85

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 7-74054839-C-T is Benign according to our data. Variant chr7-74054839-C-T is described in ClinVar as [Benign]. Clinvar id is 1297188.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELN	NM_000501.4	c.1150+70C>T		intron_variant		ENST00000252034.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELN	ENST00000252034.12	c.1150+70C>T		intron_variant		1	NM_000501.4	P4

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45480 AN: 152000 Hom.: 7943 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.343

GnomAD4 exome AF: 0.375 AC: 529334 AN: 1411840 Hom.: 103005 AF XY: 0.372 AC XY: 262239 AN XY: 705080

Gnomad4 AFR exome AF: 0.127

Gnomad4 AMR exome AF: 0.226

Gnomad4 ASJ exome AF: 0.462

Gnomad4 EAS exome AF: 0.178

Gnomad4 SAS exome AF: 0.247

Gnomad4 FIN exome AF: 0.357

Gnomad4 NFE exome AF: 0.406

Gnomad4 OTH exome AF: 0.356

GnomAD4 genome AF: 0.299 AC: 45506 AN: 152118 Hom.: 7956 Cov.: 32 AF XY: 0.294 AC XY: 21856 AN XY: 74362

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.463

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.347

Gnomad4 NFE AF: 0.401

Gnomad4 OTH AF: 0.350

Alfa AF: 0.339 Hom.: 1776

Bravo AF: 0.288

Asia WGS AF: 0.245 AC: 850 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.13
DANN	Benign	0.45

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: rs2239691; hg19: chr7-73469169;