Variant rs28763986 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000501.4(ELN):c.1414+24C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 1,611,374 control chromosomes in the GnomAD database, including 259,425 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 28146 hom., cov: 31)

Exomes 𝑓: 0.56 ( 231279 hom. )

Consequence

ELN
NM_000501.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.37

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 7-74057720-C-T is Benign according to our data. Variant chr7-74057720-C-T is described in ClinVar as [Benign]. Clinvar id is 1249499.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELN	NM_000501.4 linkuse as main transcript	c.1414+24C>T		intron_variant		ENST00000252034.12	NP_000492.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELN	ENST00000252034.12 linkuse as main transcript	c.1414+24C>T		intron_variant		1	NM_000501.4	ENSP00000252034	P4	P15502-2

Frequencies

GnomAD3 genomes

AF:

0.604

AC:

91768

AN:

151840

Hom.:

28115

Cov.:

show subpopulations

Gnomad AFR

AF:

0.694

Gnomad AMI

AF:

0.572

Gnomad AMR

AF:

0.576

Gnomad ASJ

AF:

0.519

Gnomad EAS

AF:

0.701

Gnomad SAS

AF:

0.682

Gnomad FIN

AF:

0.606

Gnomad MID

AF:

0.601

Gnomad NFE

AF:

0.549

Gnomad OTH

AF:

0.576

GnomAD3 exomes

AF:

0.590

AC:

147337

AN:

249772

Hom.:

44055

AF XY:

0.592

AC XY:

80147

AN XY:

135280

show subpopulations

Gnomad AFR exome

AF:

0.699

Gnomad AMR exome

AF:

0.573

Gnomad ASJ exome

AF:

0.522

Gnomad EAS exome

AF:

0.712

Gnomad SAS exome

AF:

0.672

Gnomad FIN exome

AF:

0.598

Gnomad NFE exome

AF:

0.544

Gnomad OTH exome

AF:

0.559

GnomAD4 exome

AF:

0.560

AC:

817610

AN:

1459414

Hom.:

231279

Cov.:

AF XY:

0.564

AC XY:

409615

AN XY:

726036

show subpopulations

Gnomad4 AFR exome

AF:

0.698

Gnomad4 AMR exome

AF:

0.574

Gnomad4 ASJ exome

AF:

0.521

Gnomad4 EAS exome

AF:

0.704

Gnomad4 SAS exome

AF:

0.673

Gnomad4 FIN exome

AF:

0.601

Gnomad4 NFE exome

AF:

0.540

Gnomad4 OTH exome

AF:

0.573

GnomAD4 genome

AF:

0.604

AC:

91837

AN:

151960

Hom.:

28146

Cov.:

AF XY:

0.609

AC XY:

45210

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.694

Gnomad4 AMR

AF:

0.577

Gnomad4 ASJ

AF:

0.519

Gnomad4 EAS

AF:

0.701

Gnomad4 SAS

AF:

0.680

Gnomad4 FIN

AF:

0.606

Gnomad4 NFE

AF:

0.549

Gnomad4 OTH

AF:

0.570

Alfa

AF:

0.570

Hom.:

6549

Bravo

AF:

0.606

Asia WGS

AF:

0.599

AC:

2083

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Cutis laxa, autosomal dominant 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.11

DANN

Benign

0.63

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over