chr7-74069201-C-CA

Position:

• chr7-74069201-C-CA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000501.4(ELN):​c.*501_*502insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.30 (7978 hom., cov: 0)
  • Exomes 𝑓: 0.23 (3171 hom.)
• Consequence: ELN NM_000501.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.669

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 -10 ACMG points.

• BP6: Variant 7-74069201-C-CA is Benign according to our data. Variant chr7-74069201-C-CA is described in ClinVar as [Benign]. Clinvar id is 360671.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELN	NM_000501.4	c.*501_*502insA		3_prime_UTR_variant	33/33	ENST00000252034.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELN	ENST00000252034.12	c.*501_*502insA		3_prime_UTR_variant	33/33	1	NM_000501.4	P4

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45070 AN: 151896 Hom.: 7938 Cov.: 0

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.0800

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.282

GnomAD4 exome AF: 0.229 AC: 24243 AN: 105850 Hom.: 3171 Cov.: 0 AF XY: 0.228 AC XY: 11510 AN XY: 50420

Gnomad4 AFR exome AF: 0.485

Gnomad4 AMR exome AF: 0.206

Gnomad4 ASJ exome AF: 0.182

Gnomad4 EAS exome AF: 0.101

Gnomad4 SAS exome AF: 0.243

Gnomad4 FIN exome AF: 0.139

Gnomad4 NFE exome AF: 0.240

Gnomad4 OTH exome AF: 0.252

GnomAD4 genome AF: 0.297 AC: 45157 AN: 152014 Hom.: 7978 Cov.: 0 AF XY: 0.290 AC XY: 21550 AN XY: 74316

Gnomad4 AFR AF: 0.492

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.0799

Gnomad4 SAS AF: 0.257

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.278

Alfa AF: 0.270 Hom.: 757

Bravo AF: 0.307

Asia WGS AF: 0.202 AC: 701 AN: 3478

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

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: rs34208922; hg19: chr7-73483531; COSMIC: COSV52706606; COSMIC: COSV52706606;