Genetic Variant ENST00000380562.8:c.1433G>A (chr7-74059886-G-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The ENST00000380562.8(ELN):c.1433G>A(p.Gly478Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ELN
ENST00000380562.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.27

Publications

0 publications found

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-AS1 (HGNC:40212): (ELN antisense RNA 1)

ELN-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.806

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000380562.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ELN	NM_000501.4	MANE Select	c.1415G>A	p.Gly472Glu	missense splice_region	Exon 23 of 33	NP_000492.2	P15502-2
ELN	NM_001278915.2		c.1433G>A	p.Gly478Glu	missense	Exon 23 of 33	NP_001265844.1	P15502-1
ELN	NM_001278939.2		c.1502G>A	p.Gly501Glu	missense splice_region	Exon 24 of 34	NP_001265868.1	P15502-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ELN	ENST00000380562.8	TSL:1	c.1433G>A	p.Gly478Glu	missense	Exon 23 of 33	ENSP00000369936.4	P15502-1
ELN	ENST00000252034.12	TSL:1 MANE Select	c.1415G>A	p.Gly472Glu	missense splice_region	Exon 23 of 33	ENSP00000252034.7	P15502-2
ELN	ENST00000458204.5	TSL:1	c.1385G>A	p.Gly462Glu	missense splice_region	Exon 22 of 32	ENSP00000403162.1	E7EN65

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1053394

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

542312

African (AFR)

AF:

0.00

AC:

AN:

25602

American (AMR)

AF:

0.00

AC:

AN:

44246

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23590

East Asian (EAS)

AF:

0.00

AC:

AN:

37820

South Asian (SAS)

AF:

0.00

AC:

AN:

78398

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53272

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4996

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

738572

Other (OTH)

AF:

0.00

AC:

AN:

46898

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Supravalvar aortic stenosis (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.94

BayesDel_addAF

Uncertain

0.087

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.41

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.30

M_CAP

Benign

0.050

MetaRNN

Pathogenic

0.78

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.0

PhyloP100

3.3

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-3.3

REVEL

Uncertain

0.33

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.87

MutPred

0.32

Loss of MoRF binding (P = 0.0456)

MVP

0.78

MPC

0.24

ClinPred

0.57

GERP RS

3.7

Varity_R

0.16

gMVP

0.49

Mutation Taster

=67/33

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over