7-74028224-G-A

Position:

chr7-74028224-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000501.4(ELN):c.37G>A(p.Val13Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,610,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ELN
NM_000501.4 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 2.16

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21375254).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELN	NM_000501.4 linkuse as main transcript	c.37G>A	p.Val13Ile	missense_variant	1/33	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.37G>A	p.Val13Ile	missense_variant	1/33	1	NM_000501.4	ENSP00000252034	P4	P15502-2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152124

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:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000828

AC:

AN:

241466

Hom.:

AF XY:

0.0000151

AC XY:

AN XY:

132178

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 SAS exome

AF:

0.0000659

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1458872

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725780

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152124

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000829

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ELN-related disorder

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 26, 2024

The ELN c.37G>A variant is predicted to result in the amino acid substitution p.Val13Ile. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0066% of alleles in individuals of South Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.076

T;T;.;T;T;T;.;T;.;.;.;.;T;.;.;.;.;.;.;T;.

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.86

D;T;D;D;T;T;D;D;T;D;T;T;T;D;D;T;D;T;T;D;D

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.21

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.53

MutationAssessor

Benign

1.8

.;.;L;L;.;.;.;.;.;L;L;L;.;L;.;L;.;L;L;.;L

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N;N;N;N;N;N;N;N

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.12

N;.;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.20

Sift

Pathogenic

0.0

D;.;D;D;D;D;D;D;D;.;D;D;D;D;D;D;D;.;D;D;D

Sift4G

Benign

0.36

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

Polyphen

0.21

B;B;B;.;.;B;.;.;B;B;B;B;B;B;.;B;.;B;B;.;.

Vest4

0.24

MutPred

0.22

Loss of catalytic residue at V13 (P = 0.0132);Loss of catalytic residue at V13 (P = 0.0132);Loss of catalytic residue at V13 (P = 0.0132);Loss of catalytic residue at V13 (P = 0.0132);Loss of catalytic residue at V13 (P = 0.0132);Loss of catalytic residue at V13 (P = 0.0132);Loss of catalytic residue at V13 (P = 0.0132);Loss of catalytic residue at V13 (P = 0.0132);Loss of catalytic residue at V13 (P = 0.0132);Loss of catalytic residue at V13 (P = 0.0132);Loss of catalytic residue at V13 (P = 0.0132);Loss of catalytic residue at V13 (P = 0.0132);Loss of catalytic residue at V13 (P = 0.0132);Loss of catalytic residue at V13 (P = 0.0132);Loss of catalytic residue at V13 (P = 0.0132);Loss of catalytic residue at V13 (P = 0.0132);Loss of catalytic residue at V13 (P = 0.0132);Loss of catalytic residue at V13 (P = 0.0132);Loss of catalytic residue at V13 (P = 0.0132);Loss of catalytic residue at V13 (P = 0.0132);Loss of catalytic residue at V13 (P = 0.0132);

MVP

0.80

MPC

0.15

ClinPred

0.43

GERP RS

2.7

Varity_R

0.035

gMVP

0.14

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