Submissions for variant NM_000718.4(CACNA1B):c.4308+7G>A

gnomAD frequency: 0.00063  dbSNP: rs192240294

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000907451	SCV001052159	likely benign	not provided	2025-01-28	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004526786	SCV005039818	uncertain significance	not specified	2024-03-18	criteria provided, single submitter	clinical testing	Variant summary: CACNA1B c.4308+7G>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00048 in 249152 control chromosomes. This frequency does not allow for any conclusion about variant significance. However, Neurodevelopmental Disorder With Seizures And Nonepileptic Hyperkinetic Movements is expected to cause severe, early-onset phenotypes, and this variant has been reported in one homozygous adult in the All Of Us database, suggesting that it may have a benign role in association with this condition. To our knowledge, no occurrence of c.4308+7G>A in individuals affected with Neurodevelopmental Disorder With Seizures And Nonepileptic Hyperkinetic Movements and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 732326). Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
CeGaT Center for Human Genetics Tuebingen	RCV000907451	SCV005891135	likely benign	not provided	2025-02-01	criteria provided, single submitter	clinical testing	CACNA1B: BP4