ClinVar Miner

Submissions for variant NM_000080.4(CHRNE):c.-95G>A

gnomAD frequency: 0.00003  dbSNP: rs990457690
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000529337 SCV000641262 pathogenic Congenital myasthenic syndrome 4A 2023-08-29 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 465866). For these reasons, this variant has been classified as Pathogenic. Adjacent variants within the N-box (c.-94G>A, c.-96C>T) have also been observed to segregate with congenital myasthenic syndrome in affected families (PMID: 10211467, 11960891) and functional studies show that they affect CHRNE expression (PMID: 8663316, 9606190). This suggests that the N-box is important for CHRNE expression, and that other variants in this motif may also be pathogenic. This variant affects a highly conserved nucleotide within the N-box motif of the CHRNE promoter region of CHRNE termed the N-box. Experimental studies show that variants affecting the N-box motif impair DNA-binding efficiency and epsilon subunit transcription, which drives synapse-specific CHRNE expression (PMID: 8663316, 9606190). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. This variant is also known as -155G>A. This variant has been observed in individuals with autosomal recessive congenital myasthenic syndrome (PMID: 10382905). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (no rsID available, gnomAD 0.02%). This variant occurs in a non-coding region of the CHRNE gene. It does not change the encoded amino acid sequence of the CHRNE protein.
Baylor Genetics RCV001328996 SCV001520276 likely pathogenic Congenital myasthenic syndrome 4B 2019-12-12 criteria provided, single submitter clinical testing This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
CeGaT Center for Human Genetics Tuebingen RCV001726226 SCV001961647 likely pathogenic not provided 2021-09-01 criteria provided, single submitter clinical testing
Baylor Genetics RCV000529337 SCV004214267 likely pathogenic Congenital myasthenic syndrome 4A 2024-02-22 criteria provided, single submitter clinical testing
GeneDx RCV001726226 SCV005202115 uncertain significance not provided 2023-06-06 criteria provided, single submitter clinical testing Previously reported in an individual with congenital myasthenia syndrome who had a second CHRNE variant; however segregation information was not reported (PMID: 33756069); Published functional studies suggest that the variant is located in a promoter region of CHRNE and results in reduced gene expression (PMID: 8663316); Also known as c.-155G>A; This variant is associated with the following publications: (PMID: 8663316, 33756069, 10382905)

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