Variant rs3757587 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000501.4(ELN):c.2087-34C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,613,298 control chromosomes in the GnomAD database, including 12,147 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.12 ( 1039 hom., cov: 31)

Exomes 𝑓: 0.12 ( 11108 hom. )

Consequence

ELN
NM_000501.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.687

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 -14 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 0 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 7-74066698-C-T is Benign according to our data. Variant chr7-74066698-C-T is described in ClinVar as [Benign]. Clinvar id is 1236531.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELN	NM_000501.4 linkuse as main transcript	c.2087-34C>T		intron_variant		ENST00000252034.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELN	ENST00000252034.12 linkuse as main transcript	c.2087-34C>T		intron_variant		1	NM_000501.4	P4	P15502-2

Frequencies

GnomAD3 genomes

AF:

0.115

AC:

17548

AN:

152118

Hom.:

1040

Cov.:

show subpopulations

Gnomad AFR

AF:

0.131

Gnomad AMI

AF:

0.190

Gnomad AMR

AF:

0.0911

Gnomad ASJ

AF:

0.0760

Gnomad EAS

AF:

0.0526

Gnomad SAS

AF:

0.0890

Gnomad FIN

AF:

0.0985

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.122

Gnomad OTH

AF:

0.109

GnomAD3 exomes

AF:

0.105

AC:

26438

AN:

251286

Hom.:

1501

AF XY:

0.105

AC XY:

14304

AN XY:

135806

show subpopulations

Gnomad AFR exome

AF:

0.134

Gnomad AMR exome

AF:

0.0820

Gnomad ASJ exome

AF:

0.0826

Gnomad EAS exome

AF:

0.0492

Gnomad SAS exome

AF:

0.0930

Gnomad FIN exome

AF:

0.0913

Gnomad NFE exome

AF:

0.125

Gnomad OTH exome

AF:

0.108

GnomAD4 exome

AF:

0.120

AC:

175147

AN:

1461064

Hom.:

11108

Cov.:

AF XY:

0.119

AC XY:

86352

AN XY:

726818

show subpopulations

Gnomad4 AFR exome

AF:

0.133

Gnomad4 AMR exome

AF:

0.0815

Gnomad4 ASJ exome

AF:

0.0840

Gnomad4 EAS exome

AF:

0.0446

Gnomad4 SAS exome

AF:

0.0926

Gnomad4 FIN exome

AF:

0.0933

Gnomad4 NFE exome

AF:

0.129

Gnomad4 OTH exome

AF:

0.107

GnomAD4 genome

AF:

0.115

AC:

17554

AN:

152234

Hom.:

1039

Cov.:

AF XY:

0.114

AC XY:

8504

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.131

Gnomad4 AMR

AF:

0.0910

Gnomad4 ASJ

AF:

0.0760

Gnomad4 EAS

AF:

0.0527

Gnomad4 SAS

AF:

0.0889

Gnomad4 FIN

AF:

0.0985

Gnomad4 NFE

AF:

0.122

Gnomad4 OTH

AF:

0.107

Alfa

AF:

0.113

Hom.:

856

Bravo

AF:

0.115

Asia WGS

AF:

0.0760

AC:

264

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

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

-0.89

CADD

Benign

1.1

DANN

Benign

0.47

BranchPoint Hunter

0.0

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