ClinVar Miner

Submissions for variant NM_000744.7(CHRNA4):c.1217C>T (p.Pro406Leu)

gnomAD frequency: 0.00002  dbSNP: rs777222517
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV001311995 SCV001502403 likely benign not provided 2022-08-01 criteria provided, single submitter clinical testing CHRNA4: BP4
Labcorp Genetics (formerly Invitae), Labcorp RCV002071872 SCV002489544 likely benign Autosomal dominant nocturnal frontal lobe epilepsy 2024-04-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV004034243 SCV004924611 uncertain significance Inborn genetic diseases 2024-02-05 criteria provided, single submitter clinical testing The c.1217C>T (p.P406L) alteration is located in exon 5 (coding exon 5) of the CHRNA4 gene. This alteration results from a C to T substitution at nucleotide position 1217, causing the proline (P) at amino acid position 406 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004800972 SCV005422855 uncertain significance not specified 2024-10-29 criteria provided, single submitter clinical testing Variant summary: CHRNA4 c.1217C>T (p.Pro406Leu) results in a non-conservative amino acid change located in the Neurotransmitter-gated ion-channel ligand-binding domain (IPR006202) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.3e-05 in 225082 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1217C>T in individuals affected with Epilepsy, Nocturnal Frontal Lobe, Type 1 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 1013459). Based on the evidence outlined above, the variant was classified as uncertain significance.

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