Submissions for variant NM_001243133.2(NLRP3):c.2834+1G>A

dbSNP: rs1572228102

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV001027795	SCV001190405	uncertain significance	Chronic infantile neurological, cutaneous and articular syndrome; Familial amyloid nephropathy with urticaria AND deafness; Familial cold autoinflammatory syndrome 1	2019-08-07	criteria provided, single submitter	clinical testing	NLRP3 NM_004895.4 exon 7 c.2840+1G>A: This variant has not been reported in the literature and is not present in large control databases. Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. Of note, this variant alters the consensus splice sequence (+/- 1,2) which is predicted to result in an absent or abnormal protein. However, loss of function variants have not been established as a known mechanism of disease for this gene; gain of function mutations are most commonly reported in association with disease in this gene (de Torre-Minguela 2017 PMID:28191008). In summary, data on this variant is suspicious for disease, but requires further evidence for pathogenicity. Therefore, the clinical significance of this variant is uncertain.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV003224506	SCV003920287	uncertain significance	Chronic infantile neurological, cutaneous and articular syndrome; Keratitis fugax hereditaria; Familial amyloid nephropathy with urticaria AND deafness; Familial cold autoinflammatory syndrome 1; Hearing loss, autosomal dominant 34, with or without inflammation	2021-03-30	criteria provided, single submitter	clinical testing	NLRP3 NM_004895.4 exon 7 c.2840+1G>A: This variant has not been reported in the literature and is not present in large control databases. Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. Of note, this variant alters the consensus splice sequence (+/- 1,2) which is predicted to result in an absent or abnormal protein. However, loss of function variants have not been established as a known mechanism of disease for this gene; gain of function mutations are most commonly reported in association with disease in this gene (de Torre-Minguela 2017 PMID:28191008). In summary, data on this variant is suspicious for disease, but requires further evidence for pathogenicity. Therefore, the clinical significance of this variant is uncertain.