Genetic Variant ELN:p.Pro9Gln (chr7-74028213-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_000501.4(ELN):c.26C>A(p.Pro9Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,611,260 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ELN
NM_000501.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.129

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 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=0.08746213).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELN	NM_000501.4 link	c.26C>A	p.Pro9Gln	missense_variant	Exon 1 of 33	ENST00000252034.12	NP_000492.2	P15502-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELN	ENST00000252034.12 link	c.26C>A	p.Pro9Gln	missense_variant	Exon 1 of 33	1	NM_000501.4	ENSP00000252034.7		P15502-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152176

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459084

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725908

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74338

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:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.20

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

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.63

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

M_CAP

Uncertain

0.099

MetaRNN

Benign

0.087

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

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.5

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

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-2.5

N;.;D;N;D;N;D;D;N;D;N;N;N;D;D;D;D;N;N;D;N

REVEL

Benign

0.16

Sift

Pathogenic

0.0

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

Sift4G

Benign

0.53

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

Polyphen

0.016

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

Vest4

0.25

MutPred

0.24

Loss of disorder (P = 0.0514);Loss of disorder (P = 0.0514);Loss of disorder (P = 0.0514);Loss of disorder (P = 0.0514);Loss of disorder (P = 0.0514);Loss of disorder (P = 0.0514);Loss of disorder (P = 0.0514);Loss of disorder (P = 0.0514);Loss of disorder (P = 0.0514);Loss of disorder (P = 0.0514);Loss of disorder (P = 0.0514);Loss of disorder (P = 0.0514);Loss of disorder (P = 0.0514);Loss of disorder (P = 0.0514);Loss of disorder (P = 0.0514);Loss of disorder (P = 0.0514);Loss of disorder (P = 0.0514);Loss of disorder (P = 0.0514);Loss of disorder (P = 0.0514);Loss of disorder (P = 0.0514);Loss of disorder (P = 0.0514);

MVP

0.30

MPC

0.17

ClinPred

0.099

GERP RS

-1.9

Varity_R

0.021

gMVP

0.18

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over