rs2301994

Variant names:

• chr7-74037933-G-A
• rs2301994
• NM_000501.4:c.196+194G>A

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.196+194G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0841 in 731,356 control chromosomes in the GnomAD database, including 3,659 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1334 hom., cov: 32)
  • Exomes 𝑓: 0.077 (2325 hom.)
• Consequence: ELN NM_000501.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.963

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=-0.86).
• BP6: Variant 7-74037933-G-A is Benign according to our data. Variant chr7-74037933-G-A is described in ClinVar as [Benign]. Clinvar id is 674889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELN	NM_000501.4	c.196+194G>A		intron_variant	Intron 4 of 32	ENST00000252034.12	NP_000492.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELN	ENST00000252034.12	c.196+194G>A		intron_variant	Intron 4 of 32	1	NM_000501.4	ENSP00000252034.7

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17135 AN: 152032 Hom.: 1329 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0274

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0962

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0563

Gnomad OTH AF: 0.0923

GnomAD4 exome AF: 0.0766 AC: 44385 AN: 579206 Hom.: 2325 Cov.: 7 AF XY: 0.0772 AC XY: 23455 AN XY: 303808

Gnomad4 AFR exome AF: 0.212

Gnomad4 AMR exome AF: 0.117

Gnomad4 ASJ exome AF: 0.0312

Gnomad4 EAS exome AF: 0.206

Gnomad4 SAS exome AF: 0.110

Gnomad4 FIN exome AF: 0.0826

Gnomad4 NFE exome AF: 0.0546

Gnomad4 OTH exome AF: 0.0835

GnomAD4 genome AF: 0.113 AC: 17150 AN: 152150 Hom.: 1334 Cov.: 32 AF XY: 0.115 AC XY: 8575 AN XY: 74374

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.0274

Gnomad4 EAS AF: 0.210

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.0962

Gnomad4 NFE AF: 0.0563

Gnomad4 OTH AF: 0.0923

Alfa AF: 0.0722 Hom.: 254

Bravo AF: 0.119

Asia WGS AF: 0.174 AC: 603 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 18, 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.3
DANN	Benign	0.70

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: rs2301994; hg19: chr7-73452263;