chr7-74059924-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_000501.4(ELN):c.1453G>A(p.Val485Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000699 in 1,574,288 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V485L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000063 ( 0 hom. )

Consequence

ELN
NM_000501.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.851

Publications

2 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.15448669).

BS2

High AC in GnomAdExome4 at 9 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000501.4. 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.1453G>A	p.Val485Met	missense	Exon 23 of 33	NP_000492.2	P15502-2
ELN	NM_001278939.2		c.1540G>A	p.Val514Met	missense	Exon 24 of 34	NP_001265868.1	P15502-3
ELN	NM_001278915.2		c.1471G>A	p.Val491Met	missense	Exon 23 of 33	NP_001265844.1	P15502-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ELN	ENST00000252034.12	TSL:1 MANE Select	c.1453G>A	p.Val485Met	missense	Exon 23 of 33	ENSP00000252034.7	P15502-2
ELN	ENST00000380562.8	TSL:1	c.1471G>A	p.Val491Met	missense	Exon 23 of 33	ENSP00000369936.4	P15502-1
ELN	ENST00000458204.5	TSL:1	c.1423G>A	p.Val475Met	missense	Exon 22 of 32	ENSP00000403162.1	E7EN65

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151668

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000795

AC:

AN:

251476

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000633

AC:

AN:

1422620

Hom.:

Cov.:

AF XY:

0.00000845

AC XY:

AN XY:

709914

show subpopulations

African (AFR)

AF:

0.0000306

AC:

AN:

32682

American (AMR)

AF:

0.00

AC:

AN:

44660

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25624

East Asian (EAS)

AF:

0.00

AC:

AN:

39500

South Asian (SAS)

AF:

0.00

AC:

AN:

85448

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5686

European-Non Finnish (NFE)

AF:

0.00000743

AC:

AN:

1076584

Other (OTH)

AF:

0.00

AC:

AN:

59032

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151668

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74052

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41286

American (AMR)

AF:

0.00

AC:

AN:

15222

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3432

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4780

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10578

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000295

AC:

AN:

67878

Other (OTH)

AF:

0.00

AC:

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions as Germline

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

0.58

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.12

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.022

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.013

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

0.85

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.0

REVEL

Benign

0.12

Sift

Benign

0.070

Sift4G

Benign

0.10

Polyphen

1.0

Vest4

0.30

MutPred

0.28

Gain of MoRF binding (P = 0.5309)

MVP

0.46

MPC

0.18

ClinPred

0.099

GERP RS

2.2

Varity_R

0.034

gMVP

0.29

Mutation Taster

=98/2

polymorphism

(source)

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

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over