rs13239907

Variant names:

• chr7-74042520-G-A
• rs13239907
• NM_000501.4:c.233-94G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000501.4(ELN):​c.233-94G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 1,080,560 control chromosomes in the GnomAD database, including 11,207 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.095 (1350 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9857 hom.)
• Consequence: ELN NM_000501.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.343
• Publications: 7 publications found

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]

ELN Gene-Disease associations (from GenCC):

• cutis laxa, autosomal dominant 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, Genomics England PanelApp, G2P
• supravalvular aortic stenosis

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• autosomal dominant cutis laxa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• familial thoracic aortic aneurysm and aortic dissection

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000306359 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 7-74042520-G-A is Benign according to our data. Variant chr7-74042520-G-A is described in ClinVar as Benign. ClinVar VariationId is 674689.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELN	NM_000501.4	c.233-94G>A		intron_variant	Intron 5 of 32	ENST00000252034.12	NP_000492.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELN	ENST00000252034.12	c.233-94G>A		intron_variant	Intron 5 of 32	1	NM_000501.4	ENSP00000252034.7

Frequencies

GnomAD3 genomes AF: 0.0956 AC: 14535 AN: 152096 Hom.: 1347 Cov.: 32

Gnomad AFR AF: 0.0226

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.0891

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.0662

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0814

Gnomad OTH AF: 0.0963

GnomAD4 exome AF: 0.114 AC: 105956 AN: 928348 Hom.: 9857 AF XY: 0.118 AC XY: 56359 AN XY: 476790

African (AFR) AF: 0.0190 AC: 439 AN: 23062

American (AMR) AF: 0.329 AC: 12798 AN: 38864

Ashkenazi Jewish (ASJ) AF: 0.0868 AC: 1715 AN: 19756

East Asian (EAS) AF: 0.366 AC: 13530 AN: 36964

South Asian (SAS) AF: 0.254 AC: 17414 AN: 68624

European-Finnish (FIN) AF: 0.0656 AC: 2816 AN: 42902

Middle Eastern (MID) AF: 0.0819 AC: 248 AN: 3028

European-Non Finnish (NFE) AF: 0.0801 AC: 52319 AN: 652962

Other (OTH) AF: 0.111 AC: 4677 AN: 42186

GnomAD4 genome AF: 0.0955 AC: 14530 AN: 152212 Hom.: 1350 Cov.: 32 AF XY: 0.103 AC XY: 7654 AN XY: 74420

African (AFR) AF: 0.0226 AC: 938 AN: 41552

American (AMR) AF: 0.225 AC: 3445 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0891 AC: 309 AN: 3468

East Asian (EAS) AF: 0.386 AC: 1992 AN: 5162

South Asian (SAS) AF: 0.270 AC: 1303 AN: 4822

European-Finnish (FIN) AF: 0.0662 AC: 702 AN: 10612

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0814 AC: 5534 AN: 67996

Other (OTH) AF: 0.0953 AC: 201 AN: 2110

Alfa AF: 0.0864 Hom.: 145

Bravo AF: 0.103

Asia WGS AF: 0.266 AC: 928 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.69
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13239907; hg19: chr7-73456850; COSMIC: COSV52709687; COSMIC: COSV52709687;