rs2275495
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_003640.5(ELP1):c.3285+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,610,484 control chromosomes in the GnomAD database, including 15,406 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.18 ( 3203 hom., cov: 32)
Exomes 𝑓: 0.12 ( 12203 hom. )
Consequence
ELP1
NM_003640.5 intron
NM_003640.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.47
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 9-108882116-G-A is Benign according to our data. Variant chr9-108882116-G-A is described in ClinVar as [Benign]. Clinvar id is 137582.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-108882116-G-A is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ELP1 | NM_003640.5 | c.3285+9C>T | intron_variant | ENST00000374647.10 | |||
ELP1 | NM_001318360.2 | c.2943+9C>T | intron_variant | ||||
ELP1 | NM_001330749.2 | c.2238+9C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ELP1 | ENST00000374647.10 | c.3285+9C>T | intron_variant | 1 | NM_003640.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.180 AC: 27408AN: 151914Hom.: 3199 Cov.: 32
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GnomAD3 exomes AF: 0.143 AC: 35712AN: 250548Hom.: 3235 AF XY: 0.133 AC XY: 17959AN XY: 135468
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GnomAD4 exome AF: 0.120 AC: 175196AN: 1458452Hom.: 12203 Cov.: 30 AF XY: 0.118 AC XY: 85356AN XY: 725754
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GnomAD4 genome AF: 0.180 AC: 27433AN: 152032Hom.: 3203 Cov.: 32 AF XY: 0.181 AC XY: 13455AN XY: 74334
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 07, 2014 | 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. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Familial dysautonomia Benign:2
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Aug 09, 2017 | - - |
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 | Invitae | Feb 01, 2024 | - - |
Computational scores
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BayesDel_noAF
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DANN
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Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at