chr10-18539734-G-T

Variant names:

• chr10-18539734-G-T
• rs4747352
• NM_201596.3:c.*10G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_201596.3(CACNB2):​c.*10G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.781 in 1,575,568 control chromosomes in the GnomAD database, including 482,573 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.76 (42251 hom., cov: 25)
  • Exomes 𝑓: 0.78 (440322 hom.)
• Consequence: CACNB2 NM_201596.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.117
• Publications: 13 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

CACNB2-AS1 (HGNC:58168):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 10-18539734-G-T is Benign according to our data. Variant chr10-18539734-G-T is described in ClinVar as Benign. ClinVar VariationId is 215549.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.945 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.*10G>T		3_prime_UTR	Exon 14 of 14	NP_963890.2	Q08289-1
	CACNB2	NM_201590.3	MANE Plus Clinical	c.*10G>T		3_prime_UTR	Exon 13 of 13	NP_963884.2	Q08289-3
	CACNB2	NM_201597.3		c.*10G>T		3_prime_UTR	Exon 14 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.*10G>T		3_prime_UTR	Exon 14 of 14	ENSP00000320025.8	Q08289-1
	CACNB2	ENST00000377329.10	TSL:1 MANE Plus Clinical	c.*10G>T		3_prime_UTR	Exon 13 of 13	ENSP00000366546.4	Q08289-3
	CACNB2	ENST00000282343.13	TSL:1	c.*10G>T		3_prime_UTR	Exon 14 of 14	ENSP00000282343.8	Q08289-4

Frequencies

GnomAD3 genomes AF: 0.757 AC: 111302 AN: 147104 Hom.: 42256 Cov.: 25

Gnomad AFR AF: 0.673

Gnomad AMI AF: 0.770

Gnomad AMR AF: 0.745

Gnomad ASJ AF: 0.726

Gnomad EAS AF: 0.968

Gnomad SAS AF: 0.782

Gnomad FIN AF: 0.772

Gnomad MID AF: 0.762

Gnomad NFE AF: 0.790

Gnomad OTH AF: 0.752

GnomAD2 exomes AF: 0.782 AC: 167924 AN: 214756 AF XY: 0.782

Gnomad AFR exome AF: 0.663

Gnomad AMR exome AF: 0.761

Gnomad ASJ exome AF: 0.734

Gnomad EAS exome AF: 0.973

Gnomad FIN exome AF: 0.770

Gnomad NFE exome AF: 0.783

Gnomad OTH exome AF: 0.767

GnomAD4 exome AF: 0.784 AC: 1119864 AN: 1428426 Hom.: 440322 Cov.: 46 AF XY: 0.784 AC XY: 556743 AN XY: 710170

African (AFR) AF: 0.656 AC: 20576 AN: 31388

American (AMR) AF: 0.764 AC: 28794 AN: 37682

Ashkenazi Jewish (ASJ) AF: 0.742 AC: 18541 AN: 24994

East Asian (EAS) AF: 0.973 AC: 38546 AN: 39596

South Asian (SAS) AF: 0.772 AC: 61952 AN: 80268

European-Finnish (FIN) AF: 0.775 AC: 38805 AN: 50040

Middle Eastern (MID) AF: 0.723 AC: 3959 AN: 5474

European-Non Finnish (NFE) AF: 0.785 AC: 863700 AN: 1100134

Other (OTH) AF: 0.765 AC: 44991 AN: 58850

GnomAD4 genome AF: 0.756 AC: 111299 AN: 147142 Hom.: 42251 Cov.: 25 AF XY: 0.755 AC XY: 53883 AN XY: 71354

African (AFR) AF: 0.673 AC: 26561 AN: 39464

American (AMR) AF: 0.745 AC: 11067 AN: 14850

Ashkenazi Jewish (ASJ) AF: 0.726 AC: 2509 AN: 3454

East Asian (EAS) AF: 0.968 AC: 4842 AN: 5002

South Asian (SAS) AF: 0.781 AC: 3671 AN: 4698

European-Finnish (FIN) AF: 0.772 AC: 7008 AN: 9074

Middle Eastern (MID) AF: 0.765 AC: 208 AN: 272

European-Non Finnish (NFE) AF: 0.790 AC: 53205 AN: 67366

Other (OTH) AF: 0.744 AC: 1532 AN: 2058

Alfa AF: 0.778 Hom.: 56311

Bravo AF: 0.745

Asia WGS AF: 0.818 AC: 2794 AN: 3420

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Brugada syndrome 4 (3)
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.0
DANN	Benign	0.67
PhyloP100		-0.12
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: rs4747352; hg19: chr10-18828663;