1-201044819-G-C

Position:

• chr1-201044819-G-C

Variant summary

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

The NM_000069.3(CACNA1S):​c.4669-363C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 152,016 control chromosomes in the GnomAD database, including 24,956 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 0.55 (24956 hom., cov: 32)
• Consequence: CACNA1S NM_000069.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA1S	NM_000069.3	c.4669-363C>G		intron_variant		ENST00000362061.4
CACNA1S	XM_005245478.4	c.4612-363C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA1S	ENST00000362061.4	c.4669-363C>G		intron_variant		1	NM_000069.3	P2

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83727 AN: 151898 Hom.: 24906 Cov.: 32

Gnomad AFR AF: 0.788

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.479

Gnomad OTH AF: 0.503

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

GnomAD4 genome AF: 0.551 AC: 83833 AN: 152016 Hom.: 24956 Cov.: 32 AF XY: 0.545 AC XY: 40475 AN XY: 74304

Gnomad4 AFR AF: 0.788

Gnomad4 AMR AF: 0.431

Gnomad4 ASJ AF: 0.454

Gnomad4 EAS AF: 0.425

Gnomad4 SAS AF: 0.327

Gnomad4 FIN AF: 0.469

Gnomad4 NFE AF: 0.479

Gnomad4 OTH AF: 0.506

Alfa AF: 0.333 Hom.: 750

Bravo AF: 0.564

Asia WGS AF: 0.425 AC: 1479 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.51
DANN	Benign	0.38

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: rs10494827; hg19: chr1-201013947;