10-18441439-C-T

Variant names:

• chr10-18441439-C-T
• rs7069923
• NM_201596.3:c.333+39396C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_201596.3(CACNB2):​c.333+39396C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 151,984 control chromosomes in the GnomAD database, including 10,059 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.36 (10059 hom., cov: 32)
• Consequence: CACNB2 NM_201596.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.463
• Publications: 11 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.497 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.333+39396C>T		intron	N/A	NP_963890.2	Q08289-1
	CACNB2	NM_201590.3	MANE Plus Clinical	c.171+39396C>T		intron	N/A	NP_963884.2	Q08289-3
	CACNB2	NM_201597.3		c.333+39396C>T		intron	N/A	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.333+39396C>T		intron	N/A	ENSP00000320025.8	Q08289-1
	CACNB2	ENST00000377329.10	TSL:1 MANE Plus Clinical	c.171+39396C>T		intron	N/A	ENSP00000366546.4	Q08289-3
	CACNB2	ENST00000352115.10	TSL:1	c.333+39396C>T		intron	N/A	ENSP00000344474.6	Q08289-8

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54444 AN: 151866 Hom.: 10044 Cov.: 32

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.358

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

GnomAD4 genome AF: 0.359 AC: 54497 AN: 151984 Hom.: 10059 Cov.: 32 AF XY: 0.355 AC XY: 26388 AN XY: 74284

African (AFR) AF: 0.435 AC: 18043 AN: 41458

American (AMR) AF: 0.290 AC: 4421 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1190 AN: 3462

East Asian (EAS) AF: 0.513 AC: 2650 AN: 5166

South Asian (SAS) AF: 0.265 AC: 1278 AN: 4814

European-Finnish (FIN) AF: 0.303 AC: 3199 AN: 10556

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.331 AC: 22512 AN: 67946

Other (OTH) AF: 0.365 AC: 771 AN: 2112

Alfa AF: 0.341 Hom.: 30986

Bravo AF: 0.365

Asia WGS AF: 0.404 AC: 1406 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.45
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs7069923; hg19: chr10-18730368;