7-74069359-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000501.4(ELN):c.*659G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 236,352 control chromosomes in the GnomAD database, including 5,790 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.21 (4881 hom., cov: 32)
  • Exomes 𝑓: 0.12 (909 hom.)
• Consequence: ELN NM_000501.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.663

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 7-74069359-G-C is Benign according to our data. Variant chr7-74069359-G-C is described in ClinVar as [Benign]. Clinvar id is 360677.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELN	NM_000501.4	c.*659G>C		3_prime_UTR_variant	33/33	ENST00000252034.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELN	ENST00000252034.12	c.*659G>C		3_prime_UTR_variant	33/33	1	NM_000501.4	P4

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31321 AN: 151944 Hom.: 4856 Cov.: 32

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.0761

Gnomad EAS AF: 0.0524

Gnomad SAS AF: 0.0914

Gnomad FIN AF: 0.0985

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.173

GnomAD4 exome AF: 0.123 AC: 10337 AN: 84290 Hom.: 909 Cov.: 0 AF XY: 0.120 AC XY: 4666 AN XY: 38994

Gnomad4 AFR exome AF: 0.441

Gnomad4 AMR exome AF: 0.112

Gnomad4 ASJ exome AF: 0.0819

Gnomad4 EAS exome AF: 0.0439

Gnomad4 SAS exome AF: 0.0835

Gnomad4 FIN exome AF: 0.0743

Gnomad4 NFE exome AF: 0.119

Gnomad4 OTH exome AF: 0.147

GnomAD4 genome AF: 0.206 AC: 31392 AN: 152062 Hom.: 4881 Cov.: 32 AF XY: 0.202 AC XY: 15012 AN XY: 74332

Gnomad4 AFR AF: 0.443

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.0761

Gnomad4 EAS AF: 0.0526

Gnomad4 SAS AF: 0.0911

Gnomad4 FIN AF: 0.0985

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.171

Alfa AF: 0.112 Hom.: 619

Bravo AF: 0.218

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Cutis laxa, autosomal dominant Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Supravalvar aortic stenosis Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.80
Dann	Benign	0.63

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: rs8326; hg19: chr7-73483689;