ClinVar Miner

Submissions for variant NM_000431.4(MVK):c.226+4A>G (rs145732290)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000216391 SCV000279116 uncertain significance not specified 2016-03-22 criteria provided, single submitter clinical testing The c.226+4 A>Gvariant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant was observed at a frequency of 0.84%, 37/4406 alleles, in individuals of African American ancestry by the NHLBI Exome Sequencing Project and in 1.21%, 13/1322 alleles in individuals of African ancestry, including 2.46%, 3/122 alleles, in individuals of African American ancestry per the 1000 Genomes Consortium. Several in-silico splice prediction models predict that c.226+4 A>G damages the natural splice donor site in intron 3, which could lead to abnormal gene splicing. However, in the absence of RNA/functional studies, the actual effect of this sequence change is unknown. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000533329 SCV000645641 benign Mevalonic aciduria; Porokeratosis 3, disseminated superficial actinic type; Hyperimmunoglobulin D with periodic fever 2020-11-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001114045 SCV001271873 likely benign Hyperimmunoglobulin D with periodic fever 2018-01-13 criteria provided, single submitter clinical testing 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Clinical Services Laboratory,Illumina RCV001114046 SCV001271874 likely benign Mevalonic aciduria 2018-01-13 criteria provided, single submitter clinical testing 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.

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