rs2239691

Variant names:

• chr7-74054839-C-T
• rs2239691
• NM_000501.4:c.1150+70C>T

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.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
• Publications: 13 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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ELN	NM_000501.4	c.1150+70C>T		intron_variant	Intron 19 of 32	ENST00000252034.12	NP_000492.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELN	ENST00000252034.12	c.1150+70C>T		intron_variant	Intron 19 of 32	1	NM_000501.4	ENSP00000252034.7

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

African (AFR) AF: 0.127 AC: 4116 AN: 32296

American (AMR) AF: 0.226 AC: 10050 AN: 44378

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 11938 AN: 25846

East Asian (EAS) AF: 0.178 AC: 6995 AN: 39406

South Asian (SAS) AF: 0.247 AC: 21043 AN: 85128

European-Finnish (FIN) AF: 0.357 AC: 18970 AN: 53110

Middle Eastern (MID) AF: 0.383 AC: 1688 AN: 4408

European-Non Finnish (NFE) AF: 0.406 AC: 433641 AN: 1068660

Other (OTH) AF: 0.356 AC: 20893 AN: 58608

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

African (AFR) AF: 0.136 AC: 5634 AN: 41528

American (AMR) AF: 0.275 AC: 4209 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 1604 AN: 3466

East Asian (EAS) AF: 0.139 AC: 721 AN: 5170

South Asian (SAS) AF: 0.236 AC: 1136 AN: 4816

European-Finnish (FIN) AF: 0.347 AC: 3667 AN: 10582

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.401 AC: 27272 AN: 67952

Other (OTH) AF: 0.350 AC: 740 AN: 2114

Alfa AF: 0.334 Hom.: 1787

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

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.13
DANN	Benign	0.45
PhyloP100		-1.8
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: rs2239691; hg19: chr7-73469169; COSMIC: COSV107249833; COSMIC: COSV107249833;