rs782585405
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP3
The NM_000501.4(ELN):c.1430_1432delTCG(p.Val477del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000369 in 1,354,424 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. V477V) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000033 ( 0 hom. )
Consequence
ELN
NM_000501.4 disruptive_inframe_deletion
NM_000501.4 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.862
Publications
0 publications found
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]
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP3
Nonframeshift variant in repetitive region in NM_000501.4
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
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ELN | MANE Select | c.1430_1432delTCG | p.Val477del | disruptive_inframe_deletion | Exon 23 of 33 | NP_000492.2 | P15502-2 | ||
| ELN | c.1517_1519delTCG | p.Val506del | disruptive_inframe_deletion | Exon 24 of 34 | NP_001265868.1 | P15502-3 | |||
| ELN | c.1448_1450delTCG | p.Val483del | disruptive_inframe_deletion | Exon 23 of 33 | NP_001265844.1 | P15502-1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ELN | TSL:1 MANE Select | c.1430_1432delTCG | p.Val477del | disruptive_inframe_deletion | Exon 23 of 33 | ENSP00000252034.7 | P15502-2 | ||
| ELN | TSL:1 | c.1448_1450delTCG | p.Val483del | disruptive_inframe_deletion | Exon 23 of 33 | ENSP00000369936.4 | P15502-1 | ||
| ELN | TSL:1 | c.1400_1402delTCG | p.Val467del | disruptive_inframe_deletion | Exon 22 of 32 | ENSP00000403162.1 | E7EN65 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000333 AC: 4AN: 1202202Hom.: 0 AF XY: 0.00000328 AC XY: 2AN XY: 610684 show subpopulations
GnomAD4 exome
AF:
AC:
4
AN:
1202202
Hom.:
AF XY:
AC XY:
2
AN XY:
610684
show subpopulations
African (AFR)
AF:
AC:
3
AN:
28406
American (AMR)
AF:
AC:
0
AN:
44396
Ashkenazi Jewish (ASJ)
AF:
AC:
1
AN:
24530
East Asian (EAS)
AF:
AC:
0
AN:
38472
South Asian (SAS)
AF:
AC:
0
AN:
81096
European-Finnish (FIN)
AF:
AC:
0
AN:
53326
Middle Eastern (MID)
AF:
AC:
0
AN:
5276
European-Non Finnish (NFE)
AF:
AC:
0
AN:
875020
Other (OTH)
AF:
AC:
0
AN:
51680
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.550
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<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 0.00000657 AC: 1AN: 152222Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74436 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152222
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74436
show subpopulations
African (AFR)
AF:
AC:
1
AN:
41548
American (AMR)
AF:
AC:
0
AN:
15288
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3468
East Asian (EAS)
AF:
AC:
0
AN:
5172
South Asian (SAS)
AF:
AC:
0
AN:
4808
European-Finnish (FIN)
AF:
AC:
0
AN:
10616
Middle Eastern (MID)
AF:
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68006
Other (OTH)
AF:
AC:
0
AN:
2110
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions
View on ClinVar Significance:Uncertain significance
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
1
-
Supravalvar aortic stenosis (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
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
Publications
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