chr10-18140454-C-T

Variant names:

• chr10-18140454-C-T
• rs55822580
• NM_201596.3:c.-283C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

CACNB2 Gene-Disease associations (from GenCC):

• Brugada syndrome 4

  Inheritance: AD, Unknown Classification: LIMITED, NO_KNOWN Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Genomics England PanelApp
• cardiogenetic disease

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• hypertrophic cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• short QT syndrome

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201596.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNB2	NM_201596.3	MANE Select	c.-283C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 14	NP_963890.2	Q08289-1
	CACNB2	NM_201596.3	MANE Select	c.-283C>T		5_prime_UTR	Exon 1 of 14	NP_963890.2	Q08289-1
	CACNB2	NM_201597.3		c.-283C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 14	NP_963891.1	Q08289-8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNB2	ENST00000324631.13	TSL:1 MANE Select	c.-283C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 14	ENSP00000320025.8	Q08289-1
	CACNB2	ENST00000324631.13	TSL:1 MANE Select	c.-283C>T		5_prime_UTR	Exon 1 of 14	ENSP00000320025.8	Q08289-1

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

African (AFR) AF: 0.0553 AC: 2295 AN: 41524

American (AMR) AF: 0.0680 AC: 1038 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0957 AC: 332 AN: 3470

East Asian (EAS) AF: 0.283 AC: 1449 AN: 5118

South Asian (SAS) AF: 0.113 AC: 544 AN: 4832

European-Finnish (FIN) AF: 0.193 AC: 2031 AN: 10528

Middle Eastern (MID) AF: 0.103 AC: 30 AN: 292

European-Non Finnish (NFE) AF: 0.0984 AC: 6684 AN: 67918

Other (OTH) AF: 0.0996 AC: 210 AN: 2108

Alfa AF: 0.102 Hom.: 117

Bravo AF: 0.0868

Asia WGS AF: 0.173 AC: 597 AN: 3464

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.2
DANN	Uncertain	0.98
PhyloP100		-1.3
PromoterAI		-0.086	Neutral

Splicing

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

Other links and lift over

dbSNP: rs55822580; hg19: chr10-18429383;