10-18140454-C-T

Position:

• chr10-18140454-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_201596.3(CACNB2):​c.-283C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0964 in 151,970 control chromosomes in the GnomAD database, including 920 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.096 (920 hom., cov: 33)
• Consequence: CACNB2 NM_201596.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.31

Genes affected

CACNB2 (HGNC:1402): (calcium voltage-gated channel auxiliary subunit beta 2) This gene encodes a subunit of a voltage-dependent calcium channel protein that is a member of the voltage-gated calcium channel superfamily. The gene product was originally identified as an antigen target in Lambert-Eaton myasthenic syndrome, an autoimmune disorder. Mutations in this gene are associated with Brugada syndrome. Alternatively spliced variants encoding different isoforms have been described. [provided by RefSeq, Feb 2013]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 10-18140454-C-T is Benign according to our data. Variant chr10-18140454-C-T is described in ClinVar as [Benign]. Clinvar id is 1291527.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNB2	NM_201596.3	c.-283C>T		5_prime_UTR_premature_start_codon_gain_variant	1/14	ENST00000324631.13	NP_963890.2
CACNB2	NM_201596.3	c.-283C>T		5_prime_UTR_variant	1/14	ENST00000324631.13	NP_963890.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNB2	ENST00000324631	c.-283C>T		5_prime_UTR_premature_start_codon_gain_variant	1/14	1	NM_201596.3	ENSP00000320025.8
CACNB2	ENST00000324631	c.-283C>T		5_prime_UTR_variant	1/14	1	NM_201596.3	ENSP00000320025.8

Frequencies

GnomAD3 genomes AF: 0.0963 AC: 14627 AN: 151856 Hom.: 912 Cov.: 33

Gnomad AFR AF: 0.0551

Gnomad AMI AF: 0.0484

Gnomad AMR AF: 0.0682

Gnomad ASJ AF: 0.0957

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.106

Gnomad NFE AF: 0.0984

Gnomad OTH AF: 0.0902

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0964 AC: 14657 AN: 151970 Hom.: 920 Cov.: 33 AF XY: 0.101 AC XY: 7525 AN XY: 74272

Gnomad4 AFR AF: 0.0553

Gnomad4 AMR AF: 0.0680

Gnomad4 ASJ AF: 0.0957

Gnomad4 EAS AF: 0.283

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.0984

Gnomad4 OTH AF: 0.0996

Alfa AF: 0.102 Hom.: 117

Bravo AF: 0.0868

Asia WGS AF: 0.173 AC: 597 AN: 3464

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.2
DANN	Uncertain	0.98

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs55822580; hg19: chr10-18429383;