chr9-108867856-G-C
Position:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_003640.5(ELP1):c.*1259C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.081 in 152,236 control chromosomes in the GnomAD database, including 669 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.081 ( 669 hom., cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
ELP1
NM_003640.5 3_prime_UTR
NM_003640.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0640
Genes affected
ELP1 (HGNC:5959): (elongator acetyltransferase complex subunit 1) The protein encoded by this gene is a scaffold protein and a regulator for three different kinases involved in proinflammatory signaling. The encoded protein can bind NF-kappa-B-inducing kinase and I-kappa-B kinases through separate domains and assemble them into an active kinase complex. Mutations in this gene have been associated with familial dysautonomia. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
Variant 9-108867856-G-C is Benign according to our data. Variant chr9-108867856-G-C is described in ClinVar as [Benign]. Clinvar id is 364539.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ELP1 | NM_003640.5 | c.*1259C>G | 3_prime_UTR_variant | 37/37 | ENST00000374647.10 | ||
ELP1 | NM_001318360.2 | c.*1259C>G | 3_prime_UTR_variant | 37/37 | |||
ELP1 | NM_001330749.2 | c.*1259C>G | 3_prime_UTR_variant | 35/35 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ELP1 | ENST00000374647.10 | c.*1259C>G | 3_prime_UTR_variant | 37/37 | 1 | NM_003640.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0809 AC: 12307AN: 152118Hom.: 668 Cov.: 33
GnomAD3 genomes
AF:
AC:
12307
AN:
152118
Hom.:
Cov.:
33
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:
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 2Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 2
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
2
Hom.:
Cov.:
0
AF XY:
AC XY:
0
AN XY:
2
Gnomad4 NFE exome
AF:
GnomAD4 genome AF: 0.0810 AC: 12337AN: 152236Hom.: 669 Cov.: 33 AF XY: 0.0845 AC XY: 6292AN XY: 74442
GnomAD4 genome
AF:
AC:
12337
AN:
152236
Hom.:
Cov.:
33
AF XY:
AC XY:
6292
AN XY:
74442
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:
Asia WGS
AF:
AC:
708
AN:
3478
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Familial dysautonomia 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
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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