rs373127841

Variant names:

• chr10-18140707-G-A
• rs373127841
• NM_201596.3:c.-30G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-18140707-G-A
• chr10-18140707-G-T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_201596.3(CACNB2):​c.-30G>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 0.000673 in 1,574,706 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00078 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00066 (13 hom.)
• Consequence: CACNB2 NM_201596.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.16
• Publications: 0 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 10-18140707-G-A is Benign according to our data. Variant chr10-18140707-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 190721.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 119 AD,Unknown gene.

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.-30G>A		5_prime_UTR	Exon 1 of 14	NP_963890.2	Q08289-1
	CACNB2	NM_201597.3		c.-30G>A		5_prime_UTR	Exon 1 of 14	NP_963891.1	Q08289-8
	CACNB2	NM_201571.4		c.-473G>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.-30G>A		5_prime_UTR	Exon 1 of 14	ENSP00000320025.8	Q08289-1
	CACNB2	ENST00000352115.10	TSL:1	c.-30G>A		upstream_gene	N/A	ENSP00000344474.6	Q08289-8
	CACNB2	ENST00000377328.5	TSL:1	c.-30G>A		upstream_gene	N/A	ENSP00000366545.1	A6PVM6

Frequencies

GnomAD3 genomes AF: 0.000789 AC: 120 AN: 152114 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000500

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00134 AC: 256 AN: 190688 AF XY: 0.00137

Gnomad AFR exome AF: 0.000297

Gnomad AMR exome AF: 0.00198

Gnomad ASJ exome AF: 0.0126

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000582

Gnomad OTH exome AF: 0.00570

GnomAD4 exome AF: 0.000661 AC: 940 AN: 1422478 Hom.: 13 Cov.: 29 AF XY: 0.000688 AC XY: 485 AN XY: 705232

African (AFR) AF: 0.000182 AC: 6 AN: 32902

American (AMR) AF: 0.00205 AC: 82 AN: 39938

Ashkenazi Jewish (ASJ) AF: 0.0129 AC: 328 AN: 25460

East Asian (EAS) AF: 0.00 AC: 0 AN: 38418

South Asian (SAS) AF: 0.000404 AC: 33 AN: 81736

European-Finnish (FIN) AF: 0.0000203 AC: 1 AN: 49220

Middle Eastern (MID) AF: 0.0132 AC: 63 AN: 4766

European-Non Finnish (NFE) AF: 0.000293 AC: 320 AN: 1091212

Other (OTH) AF: 0.00182 AC: 107 AN: 58826

GnomAD4 genome AF: 0.000782 AC: 119 AN: 152228 Hom.: 0 Cov.: 32 AF XY: 0.000887 AC XY: 66 AN XY: 74414

African (AFR) AF: 0.0000962 AC: 4 AN: 41576

American (AMR) AF: 0.00118 AC: 18 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0150 AC: 52 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5138

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 292

European-Non Finnish (NFE) AF: 0.000500 AC: 34 AN: 67982

Other (OTH) AF: 0.00331 AC: 7 AN: 2112

Alfa AF: 0.00231 Hom.: 0

Bravo AF: 0.000914

ClinVar

ClinVar submissions

Significance: Likely 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	-0.73
CADD	Benign	15
DANN	Benign	0.96
PhyloP100		1.2
PromoterAI		-0.11	Neutral
Mutation Taster		=300/0	polymorphism

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: rs373127841; hg19: chr10-18429636;