rs1536129

Positions:

• chr1-201100063-C-A
• chr1-201100063-C-G
• chr1-201100063-C-T

Variant summary

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

The NM_000069.3(CACNA1S):​c.259-6042G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 152,008 control chromosomes in the GnomAD database, including 11,518 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 0.39 (11518 hom., cov: 32)
• Consequence: CACNA1S NM_000069.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.168

Genes affected

CACNA1S (HGNC:1397): (calcium voltage-gated channel subunit alpha1 S) This gene encodes one of the five subunits of the slowly inactivating L-type voltage-dependent calcium channel in skeletal muscle cells. Mutations in this gene have been associated with hypokalemic periodic paralysis, thyrotoxic periodic paralysis and malignant hyperthermia susceptibility. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA1S	NM_000069.3	c.259-6042G>T		intron_variant		ENST00000362061.4
CACNA1S	XM_005245478.4	c.259-6042G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA1S	ENST00000362061.4	c.259-6042G>T		intron_variant		1	NM_000069.3	P2

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58576 AN: 151890 Hom.: 11507 Cov.: 32

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.386 AC: 58608 AN: 152008 Hom.: 11518 Cov.: 32 AF XY: 0.392 AC XY: 29104 AN XY: 74308

Gnomad4 AFR AF: 0.430

Gnomad4 AMR AF: 0.346

Gnomad4 ASJ AF: 0.270

Gnomad4 EAS AF: 0.394

Gnomad4 SAS AF: 0.435

Gnomad4 FIN AF: 0.449

Gnomad4 NFE AF: 0.360

Gnomad4 OTH AF: 0.354

Alfa AF: 0.367 Hom.: 3697

Bravo AF: 0.378

Asia WGS AF: 0.418 AC: 1452 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.6
DANN	Benign	0.76

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: rs1536129; hg19: chr1-201069191;