rs138094231

Variant names:

• chr10-18140695-C-A
• rs138094231
• NM_201596.3:c.-42C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-18140695-C-A
• chr10-18140695-C-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.-42C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0357 in 1,559,106 control chromosomes in the GnomAD database, including 1,150 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.042 (150 hom., cov: 32)
  • Exomes 𝑓: 0.035 (1000 hom.)
• Consequence: CACNB2 NM_201596.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.990
• Publications: 5 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 10-18140695-C-A is Benign according to our data. Variant chr10-18140695-C-A is described in ClinVar as Benign. ClinVar VariationId is 190719.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0597 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.-42C>A		5_prime_UTR	Exon 1 of 14	NP_963890.2	Q08289-1
	CACNB2	NM_201597.3		c.-42C>A		5_prime_UTR	Exon 1 of 14	NP_963891.1	Q08289-8
	CACNB2	NM_201571.4		c.-485C>A		5_prime_UTR	Exon 1 of 14	NP_963865.2	Q08289-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNB2	ENST00000324631.13	TSL:1 MANE Select	c.-42C>A		5_prime_UTR	Exon 1 of 14	ENSP00000320025.8	Q08289-1
	CACNB2	ENST00000352115.10	TSL:1	c.-42C>A		upstream_gene	N/A	ENSP00000344474.6	Q08289-8
	CACNB2	ENST00000377328.5	TSL:1	c.-42C>A		upstream_gene	N/A	ENSP00000366545.1	A6PVM6

Frequencies

GnomAD3 genomes AF: 0.0420 AC: 6384 AN: 152086 Hom.: 149 Cov.: 32

Gnomad AFR AF: 0.0616

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0281

Gnomad ASJ AF: 0.0444

Gnomad EAS AF: 0.000583

Gnomad SAS AF: 0.0344

Gnomad FIN AF: 0.0389

Gnomad MID AF: 0.0382

Gnomad NFE AF: 0.0372

Gnomad OTH AF: 0.0402

GnomAD2 exomes AF: 0.0326 AC: 5979 AN: 183408 AF XY: 0.0332

Gnomad AFR exome AF: 0.0588

Gnomad AMR exome AF: 0.0192

Gnomad ASJ exome AF: 0.0475

Gnomad EAS exome AF: 0.0000704

Gnomad FIN exome AF: 0.0361

Gnomad NFE exome AF: 0.0374

Gnomad OTH exome AF: 0.0351

GnomAD4 exome AF: 0.0350 AC: 49223 AN: 1406906 Hom.: 1000 Cov.: 27 AF XY: 0.0353 AC XY: 24619 AN XY: 697748

African (AFR) AF: 0.0611 AC: 1992 AN: 32608

American (AMR) AF: 0.0195 AC: 763 AN: 39204

Ashkenazi Jewish (ASJ) AF: 0.0478 AC: 1209 AN: 25314

East Asian (EAS) AF: 0.0000262 AC: 1 AN: 38106

South Asian (SAS) AF: 0.0346 AC: 2807 AN: 81050

European-Finnish (FIN) AF: 0.0398 AC: 1946 AN: 48856

Middle Eastern (MID) AF: 0.0457 AC: 207 AN: 4534

European-Non Finnish (NFE) AF: 0.0355 AC: 38306 AN: 1078938

Other (OTH) AF: 0.0342 AC: 1992 AN: 58296

GnomAD4 genome AF: 0.0420 AC: 6390 AN: 152200 Hom.: 150 Cov.: 32 AF XY: 0.0413 AC XY: 3072 AN XY: 74416

African (AFR) AF: 0.0617 AC: 2563 AN: 41566

American (AMR) AF: 0.0280 AC: 429 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0444 AC: 154 AN: 3466

East Asian (EAS) AF: 0.000584 AC: 3 AN: 5134

South Asian (SAS) AF: 0.0346 AC: 167 AN: 4826

European-Finnish (FIN) AF: 0.0389 AC: 412 AN: 10604

Middle Eastern (MID) AF: 0.0342 AC: 10 AN: 292

European-Non Finnish (NFE) AF: 0.0372 AC: 2529 AN: 67990

Other (OTH) AF: 0.0393 AC: 83 AN: 2112

Alfa AF: 0.0225 Hom.: 9

Bravo AF: 0.0408

Asia WGS AF: 0.0160 AC: 56 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	12
DANN	Benign	0.88
PhyloP100		-0.99
PromoterAI		-0.11	Neutral
Mutation Taster		=300/0	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: rs138094231; hg19: chr10-18429624;