Variant 7-74028150-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The ENST00000380562(ELN):c.-38C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0141 in 1,393,342 control chromosomes in the GnomAD database, including 360 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 18 hom., cov: 31)

Exomes 𝑓: 0.015 ( 342 hom. )

Consequence

ELN
ENST00000380562 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.34

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:

ELN (HGNC:):

ELN links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 7-74028150-C-T is Benign according to our data. Variant chr7-74028150-C-T is described in ClinVar as [Benign]. Clinvar id is 213168.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0798 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.-38C>T		upstream_gene_variant		ENST00000252034.12	NP_000492.2	P15502-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELN	ENST00000252034.12 linkuse as main transcript	c.-38C>T		upstream_gene_variant		1	NM_000501.4	ENSP00000252034.7		P15502-2

Frequencies

GnomAD3 genomes

AF:

0.0105

AC:

1497

AN:

142404

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00384

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0117

Gnomad ASJ

AF:

0.0168

Gnomad EAS

AF:

0.0449

Gnomad SAS

AF:

0.0869

Gnomad FIN

AF:

0.00133

Gnomad MID

AF:

0.0300

Gnomad NFE

AF:

0.00824

Gnomad OTH

AF:

0.0125

GnomAD3 exomes

AF:

0.0184

AC:

4380

AN:

237612

Hom.:

104

AF XY:

0.0215

AC XY:

2787

AN XY:

129850

show subpopulations

Gnomad AFR exome

AF:

0.00238

Gnomad AMR exome

AF:

0.0110

Gnomad ASJ exome

AF:

0.0175

Gnomad EAS exome

AF:

0.0323

Gnomad SAS exome

AF:

0.0730

Gnomad FIN exome

AF:

0.00127

Gnomad NFE exome

AF:

0.00875

Gnomad OTH exome

AF:

0.0189

GnomAD4 exome

AF:

0.0145

AC:

18195

AN:

1250810

Hom.:

342

Cov.:

AF XY:

0.0169

AC XY:

10447

AN XY:

619012

show subpopulations

Gnomad4 AFR exome

AF:

0.00390

Gnomad4 AMR exome

AF:

0.0128

Gnomad4 ASJ exome

AF:

0.0228

Gnomad4 EAS exome

AF:

0.0679

Gnomad4 SAS exome

AF:

0.0736

Gnomad4 FIN exome

AF:

0.00227

Gnomad4 NFE exome

AF:

0.00851

Gnomad4 OTH exome

AF:

0.0196

GnomAD4 genome

AF:

0.0105

AC:

1499

AN:

142532

Hom.:

Cov.:

AF XY:

0.0119

AC XY:

824

AN XY:

69050

show subpopulations

Gnomad4 AFR

AF:

0.00383

Gnomad4 AMR

AF:

0.0117

Gnomad4 ASJ

AF:

0.0168

Gnomad4 EAS

AF:

0.0447

Gnomad4 SAS

AF:

0.0873

Gnomad4 FIN

AF:

0.00133

Gnomad4 NFE

AF:

0.00824

Gnomad4 OTH

AF:

0.0129

Alfa

AF:

0.00729

Hom.:

Bravo

AF:

0.00926

Asia WGS

AF:

0.0560

AC:

195

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Cutis laxa, autosomal dominant

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Supravalvar aortic stenosis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.97

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