dbSNP rs17633541: CACNB1:c.*1436G>A (chr17-39173757-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000723.5(CACNB1):c.*1436G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.047 in 152,616 control chromosomes in the GnomAD database, including 190 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 0.047 ( 190 hom., cov: 32)

Exomes 𝑓: 0.046 ( 0 hom. )

Consequence

CACNB1
NM_000723.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.490

Publications

9 publications found

Variant links:

Genes affected

CACNB1 (HGNC:1401): (calcium voltage-gated channel auxiliary subunit beta 1) The protein encoded by this gene belongs to the calcium channel beta subunit family. It plays an important role in the calcium channel by modulating G protein inhibition, increasing peak calcium current, controlling the alpha-1 subunit membrane targeting and shifting the voltage dependence of activation and inactivation. Alternative splicing occurs at this locus and three transcript variants encoding three distinct isoforms have been identified. [provided by RefSeq, Jul 2008]

CACNB1 links:

ENSG00000266101 (HGNC:58562):

ENSG00000266101 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNB1	NM_000723.5 link	c.*1436G>A		3_prime_UTR_variant	Exon 14 of 14	ENST00000394303.8	NP_000714.3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CACNB1	ENST00000394303.8 link	c.*1436G>A	3_prime_UTR_variant	Exon 14 of 14	1	NM_000723.5	ENSP00000377840.3	Q02641-1
ENSG00000266101	ENST00000579256.1 link	n.273+195C>T	intron_variant	Intron 1 of 1	4
ENSG00000266101	ENST00000831062.1 link	n.95+3070C>T	intron_variant	Intron 1 of 2
CACNB1	ENST00000539338.6 link	n.*44G>A	downstream_gene_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0470

AC:

7150

AN:

152152

Hom.:

190

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0605

Gnomad AMI

AF:

0.0395

Gnomad AMR

AF:

0.0463

Gnomad ASJ

AF:

0.0634

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0133

Gnomad FIN

AF:

0.0129

Gnomad MID

AF:

0.0764

Gnomad NFE

AF:

0.0490

Gnomad OTH

AF:

0.0565

GnomAD4 exome

AF:

0.0462

AC:

AN:

346

Hom.:

Cov.:

AF XY:

0.0644

AC XY:

AN XY:

202

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.0441

AC:

AN:

136

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.0116

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0702

AC:

AN:

114

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.428

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0470

AC:

7154

AN:

152270

Hom.:

190

Cov.:

AF XY:

0.0445

AC XY:

3316

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.0604

AC:

2510

AN:

41552

American (AMR)

AF:

0.0462

AC:

707

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0634

AC:

220

AN:

3472

East Asian (EAS)

AF:

0.000772

AC:

AN:

5184

South Asian (SAS)

AF:

0.0133

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0129

AC:

137

AN:

10614

Middle Eastern (MID)

AF:

0.0822

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0490

AC:

3334

AN:

68022

Other (OTH)

AF:

0.0559

AC:

118

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

364

728

1092

1456

1820

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

234

312

390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0523

Hom.:

335

Bravo

AF:

0.0516

Asia WGS

AF:

0.0130

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.5

(source)

DANN

Benign

0.72

PhyloP100

0.49

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over