rs7860423

chr9-138061095-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000718.4(CACNA1B):c.4668+1358G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 152,186 control chromosomes in the GnomAD database, including 15,008 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 0.35 (15008 hom., cov: 33)
• Consequence: CACNA1B NM_000718.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA1B	NM_000718.4	c.4668+1358G>A		intron_variant		ENST00000371372.6
CACNA1B	NM_001243812.2	c.4668+1358G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA1B	ENST00000371372.6	c.4668+1358G>A		intron_variant		5	NM_000718.4	P4
CACNA1B	ENST00000277551.6	c.4668+1358G>A		intron_variant		5		A2
CACNA1B	ENST00000371357.5	c.4671+1358G>A		intron_variant		5		A2
CACNA1B	ENST00000371363.5	c.4668+1358G>A		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53773 AN: 152068 Hom.: 14953 Cov.: 33

Gnomad AFR AF: 0.761

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.657

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.305

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.354 AC: 53894 AN: 152186 Hom.: 15008 Cov.: 33 AF XY: 0.349 AC XY: 25937 AN XY: 74422

Gnomad4 AFR AF: 0.762

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.658

Gnomad4 SAS AF: 0.308

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.313

Alfa AF: 0.204 Hom.: 3668

Bravo AF: 0.375

Asia WGS AF: 0.492 AC: 1712 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.14
Dann	Benign	0.23

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

LitVar

Other links and lift over

dbSNP: rs7860423; hg19: chr9-140955547; COSMIC: COSV53119570;