rs7870040

Positions:

• chr9-137984918-C-A
• chr9-137984918-C-G

Variant summary

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

The NM_000718.4(CACNA1B):​c.1769+668C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 152,150 control chromosomes in the GnomAD database, including 7,977 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 0.27 (7977 hom., cov: 33)
• Consequence: CACNA1B NM_000718.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00600

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA1B	NM_000718.4	c.1769+668C>A		intron_variant		ENST00000371372.6	NP_000709.1
CACNA1B	NM_001243812.2	c.1769+668C>A		intron_variant			NP_001230741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA1B	ENST00000371372.6	c.1769+668C>A		intron_variant		5	NM_000718.4	ENSP00000360423	P4
CACNA1B	ENST00000277551.6	c.1769+668C>A		intron_variant		5		ENSP00000277551	A2
CACNA1B	ENST00000371357.5	c.1772+668C>A		intron_variant		5		ENSP00000360408	A2
CACNA1B	ENST00000371363.5	c.1769+668C>A		intron_variant		5		ENSP00000360414	A2

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41715 AN: 152032 Hom.: 7959 Cov.: 33

Gnomad AFR AF: 0.512

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.643

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.275 AC: 41782 AN: 152150 Hom.: 7977 Cov.: 33 AF XY: 0.273 AC XY: 20335 AN XY: 74382

Gnomad4 AFR AF: 0.512

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.644

Gnomad4 SAS AF: 0.276

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.254

Alfa AF: 0.186 Hom.: 1708

Bravo AF: 0.286

Asia WGS AF: 0.454 AC: 1582 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.6
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7870040; hg19: chr9-140879370;