rs41376344
Positions:
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBS1BS2
The NM_000501.4(ELN):c.931G>A(p.Ala311Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000573 in 1,613,572 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.00052 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00058 ( 6 hom. )
Consequence
ELN
NM_000501.4 missense
NM_000501.4 missense
Scores
1
4
12
Clinical Significance
Conservation
PhyloP100: 4.75
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -18 ACMG points.
PM1
?
In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 4 uncertain in NM_000501.4
BP4
?
Computational evidence support a benign effect (MetaRNN=0.007754147).
BP6
?
Variant 7-74051965-G-A is Benign according to our data. Variant chr7-74051965-G-A is described in ClinVar as [Benign]. Clinvar id is 360642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000519 (79/152318) while in subpopulation EAS AF= 0.013 (67/5172). AF 95% confidence interval is 0.0105. There are 1 homozygotes in gnomad4. There are 39 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 79 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ELN | NM_000501.4 | c.931G>A | p.Ala311Thr | missense_variant | 17/33 | ENST00000252034.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ELN | ENST00000252034.12 | c.931G>A | p.Ala311Thr | missense_variant | 17/33 | 1 | NM_000501.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000519 AC: 79AN: 152200Hom.: 1 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
79
AN:
152200
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00115 AC: 288AN: 250306Hom.: 4 AF XY: 0.00106 AC XY: 144AN XY: 135586
GnomAD3 exomes
AF:
AC:
288
AN:
250306
Hom.:
AF XY:
AC XY:
144
AN XY:
135586
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000578 AC: 845AN: 1461254Hom.: 6 Cov.: 31 AF XY: 0.000586 AC XY: 426AN XY: 726928
GnomAD4 exome
AF:
AC:
845
AN:
1461254
Hom.:
Cov.:
31
AF XY:
AC XY:
426
AN XY:
726928
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000519 AC: 79AN: 152318Hom.: 1 Cov.: 32 AF XY: 0.000524 AC XY: 39AN XY: 74480
GnomAD4 genome
?
AF:
AC:
79
AN:
152318
Hom.:
Cov.:
32
AF XY:
AC XY:
39
AN XY:
74480
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
?
AF:
AC:
138
Asia WGS
AF:
AC:
19
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Supravalvar aortic stenosis Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 16, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 16, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Cutis laxa, autosomal dominant 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;.;T;T;.;.;.;.;.;T;.;.;.;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;N;N;N;N;N;N;N;N;N;N;N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;N;N;N;N;N;N;N;N;N;N;N;N;N;N
REVEL
Benign
Sift
Pathogenic
D;.;D;D;D;D;D;.;D;D;D;D;D;.;D;D
Sift4G
Uncertain
D;T;D;T;T;D;T;D;T;T;D;T;T;D;D;D
Polyphen
D;D;D;.;D;.;D;D;D;D;D;D;D;D;D;.
Vest4
MVP
MPC
0.18
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at