rs8326

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_000501.4(ELN):​c.*659G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000254 in 236,408 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00028 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

ELN
NM_000501.4 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.663
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000283 (43/152102) while in subpopulation SAS AF= 0.00498 (24/4820). AF 95% confidence interval is 0.00343. There are 1 homozygotes in gnomad4. There are 25 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 43 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ELNNM_000501.4 linkuse as main transcriptc.*659G>A 3_prime_UTR_variant 33/33 ENST00000252034.12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ELNENST00000252034.12 linkuse as main transcriptc.*659G>A 3_prime_UTR_variant 33/331 NM_000501.4 P4P15502-2

Frequencies

GnomAD3 genomes
AF:
0.000283
AC:
43
AN:
151984
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000484
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000385
Gnomad SAS
AF:
0.00498
Gnomad FIN
AF:
0.0000944
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000191
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.000202
AC:
17
AN:
84306
Hom.:
0
Cov.:
0
AF XY:
0.000179
AC XY:
7
AN XY:
39002
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000874
Gnomad4 SAS exome
AF:
0.00879
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000155
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.000283
AC:
43
AN:
152102
Hom.:
1
Cov.:
32
AF XY:
0.000336
AC XY:
25
AN XY:
74352
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000386
Gnomad4 SAS
AF:
0.00498
Gnomad4 FIN
AF:
0.0000944
Gnomad4 NFE
AF:
0.000191
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
1.7
DANN
Benign
0.87

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.

Other links and lift over

dbSNP: rs8326; hg19: chr7-73483689; API