9-137882854-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong

The NM_000718.4(CACNA1B):c.501C>G(p.Asn167Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: not found (cov: 32)

Consequence

CACNA1B
NM_000718.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.13

Publications

36 publications found

Variant links:

Genes affected

CACNA1B (HGNC:1389): (calcium voltage-gated channel subunit alpha1 B) The protein encoded by this gene is the pore-forming subunit of an N-type voltage-dependent calcium channel, which controls neurotransmitter release from neurons. The encoded protein forms a complex with alpha-2, beta, and delta subunits to form the high-voltage activated channel. This channel is sensitive to omega-conotoxin-GVIA and omega-agatoxin-IIIA but insensitive to dihydropyridines. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

CACNA1B Gene-Disease associations (from GenCC):

neurodevelopmental disorder with seizures and nonepileptic hyperkinetic movements
Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
complex neurodevelopmental disorder with motor features
Inheritance: AR Classification: MODERATE Submitted by: ClinGen
undetermined early-onset epileptic encephalopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CACNA1B links:

ENSG00000203987 (HGNC:58213):

ENSG00000203987 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0038129091).

BP6

Variant 9-137882854-C-G is Benign according to our data. Variant chr9-137882854-C-G is described in ClinVar as Benign. ClinVar VariationId is 802555.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000718.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CACNA1B	NM_000718.4	MANE Select	c.501C>G	p.Asn167Lys	missense	Exon 3 of 47	NP_000709.1
CACNA1B	NM_001243812.2		c.501C>G	p.Asn167Lys	missense	Exon 3 of 47	NP_001230741.1
CACNA1B-AS2	NR_121583.1		n.2674G>C		non_coding_transcript_exon	Exon 2 of 4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CACNA1B	ENST00000371372.6	TSL:5 MANE Select	c.501C>G	p.Asn167Lys	missense	Exon 3 of 47	ENSP00000360423.1
CACNA1B	ENST00000371357.5	TSL:5	c.501C>G	p.Asn167Lys	missense	Exon 3 of 46	ENSP00000360408.1
CACNA1B	ENST00000371363.5	TSL:5	c.501C>G	p.Asn167Lys	missense	Exon 3 of 46	ENSP00000360414.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.500

AC:

124620

AN:

249262

AF XY:

0.500

show subpopulations

Gnomad AFR exome

AF:

0.500

Gnomad AMR exome

AF:

0.500

Gnomad ASJ exome

AF:

0.500

Gnomad EAS exome

AF:

0.499

Gnomad FIN exome

AF:

0.500

Gnomad NFE exome

AF:

0.500

Gnomad OTH exome

AF:

0.500

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.245

Hom.:

ExAC

AF:

0.499

AC:

60416

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Mar 30, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Neurodevelopmental disorder with seizures and nonepileptic hyperkinetic movements

Benign:1

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.040

CADD

Benign

5.3

(source)

DANN

Benign

0.90

DEOGEN2

Pathogenic

0.96

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.81

MetaRNN

Benign

0.0038

MetaSVM

Pathogenic

1.0

MutationAssessor

Pathogenic

5.0

PhyloP100

-1.1

PrimateAI

Uncertain

0.77

PROVEAN

Pathogenic

-5.4

REVEL

Pathogenic

0.75

Sift

Uncertain

0.010

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.53

MutPred

0.52

Gain of methylation at N167 (P = 0.0022)

MPC

1.0

ClinPred

0.15

GERP RS

-4.7

Varity_R

0.93

gMVP

1.0

Mutation Taster

=86/14

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over