rs2301995

chr7-74037810-G-A

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.196+71G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0771 in 1,578,610 control chromosomes in the GnomAD database, including 6,167 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1333 hom., cov: 32)
  • Exomes 𝑓: 0.073 (4834 hom.)
• Consequence: ELN NM_000501.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.144

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=-0.91).
• BP6: Variant 7-74037810-G-A is Benign according to our data. Variant chr7-74037810-G-A is described in ClinVar as [Benign]. Clinvar id is 1297183.Status of the report is criteria_provided_single_submitter, 1 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/exons	MANE	UniProt
ELN	NM_000501.4	c.196+71G>A		intron_variant		ENST00000252034.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELN	ENST00000252034.12	c.196+71G>A		intron_variant		1	NM_000501.4	P4

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17141 AN: 152064 Hom.: 1328 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: 0.210

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0966

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0563

Gnomad OTH AF: 0.0940

GnomAD4 exome AF: 0.0734 AC: 104631 AN: 1426428 Hom.: 4834 Cov.: 28 AF XY: 0.0736 AC XY: 52015 AN XY: 706824

Gnomad4 AFR exome AF: 0.220

Gnomad4 AMR exome AF: 0.123

Gnomad4 ASJ exome AF: 0.0320

Gnomad4 EAS exome AF: 0.208

Gnomad4 SAS exome AF: 0.112

Gnomad4 FIN exome AF: 0.0863

Gnomad4 NFE exome AF: 0.0592

Gnomad4 OTH exome AF: 0.0848

GnomAD4 genome AF: 0.113 AC: 17156 AN: 152182 Hom.: 1333 Cov.: 32 AF XY: 0.115 AC XY: 8588 AN XY: 74418

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.0274

Gnomad4 EAS AF: 0.210

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.0966

Gnomad4 NFE AF: 0.0563

Gnomad4 OTH AF: 0.0939

Alfa AF: 0.0769 Hom.: 303

Bravo AF: 0.119

Asia WGS AF: 0.174 AC: 602 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.6
Dann	Benign	0.50

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: rs2301995; hg19: chr7-73452140; COSMIC: COSV52706883; COSMIC: COSV52706883;