rs77481135
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000080.4(CHRNE):c.-8G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00642 in 1,613,906 control chromosomes in the GnomAD database, including 552 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.033 ( 285 hom., cov: 31)
Exomes 𝑓: 0.0036 ( 267 hom. )
Consequence
CHRNE
NM_000080.4 5_prime_UTR
NM_000080.4 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.514
Genes affected
CHRNE (HGNC:1966): (cholinergic receptor nicotinic epsilon subunit) Acetylcholine receptors at mature mammalian neuromuscular junctions are pentameric protein complexes composed of four subunits in the ratio of two alpha subunits to one beta, one epsilon, and one delta subunit. The acetylcholine receptor changes subunit composition shortly after birth when the epsilon subunit replaces the gamma subunit seen in embryonic receptors. Mutations in the epsilon subunit are associated with congenital myasthenic syndrome. [provided by RefSeq, Sep 2009]
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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=-0.85).
BP6
?
Variant 17-4903071-C-T is Benign according to our data. Variant chr17-4903071-C-T is described in ClinVar as [Benign]. Clinvar id is 254888.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHRNE | NM_000080.4 | c.-8G>A | 5_prime_UTR_variant | 1/12 | ENST00000649488.2 | ||
CHRNE | XM_017024115.2 | c.11-308G>A | intron_variant | ||||
C17orf107 | XR_007065253.1 | n.2388+950C>T | intron_variant, non_coding_transcript_variant | ||||
C17orf107 | XR_007065254.1 | n.2388+950C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRNE | ENST00000649488.2 | c.-8G>A | 5_prime_UTR_variant | 1/12 | NM_000080.4 | P1 | |||
CHRNE | ENST00000649830.1 | c.-887-308G>A | intron_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0329 AC: 5006AN: 151954Hom.: 279 Cov.: 31
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GnomAD3 exomes AF: 0.00943 AC: 2370AN: 251254Hom.: 108 AF XY: 0.00694 AC XY: 942AN XY: 135826
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GnomAD4 exome AF: 0.00364 AC: 5321AN: 1461834Hom.: 267 Cov.: 32 AF XY: 0.00318 AC XY: 2315AN XY: 727230
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GnomAD4 genome ? AF: 0.0331 AC: 5034AN: 152072Hom.: 285 Cov.: 31 AF XY: 0.0314 AC XY: 2335AN XY: 74338
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 12, 2017 | 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 | - | - - |
Congenital myasthenic syndrome Benign:2
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
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
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at