rs2275703

chr1-160195305-A-C

Variant summary

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

The NM_001231.5(CASQ1):c.578-156A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 151,768 control chromosomes in the GnomAD database, including 12,533 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 0.38 (12533 hom., cov: 30)
• Consequence: CASQ1 NM_001231.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

Genes affected

CASQ1 (HGNC:1512): (calsequestrin 1) This gene encodes the skeletal muscle specific member of the calsequestrin protein family. Calsequestrin functions as a luminal sarcoplasmic reticulum calcium sensor in both cardiac and skeletal muscle cells. This protein, also known as calmitine, functions as a calcium regulator in the mitochondria of skeletal muscle. This protein is absent in patients with Duchenne and Becker types of muscular dystrophy. [provided by RefSeq, Jun 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASQ1	NM_001231.5	c.578-156A>C		intron_variant		ENST00000368078.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASQ1	ENST00000368078.8	c.578-156A>C		intron_variant		1	NM_001231.5	P1
CASQ1	ENST00000481081.1	n.463-156A>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58183 AN: 151650 Hom.: 12529 Cov.: 30

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.419

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

GnomAD4 genome AF: 0.384 AC: 58213 AN: 151768 Hom.: 12533 Cov.: 30 AF XY: 0.380 AC XY: 28183 AN XY: 74136

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.422

Gnomad4 ASJ AF: 0.432

Gnomad4 EAS AF: 0.201

Gnomad4 SAS AF: 0.399

Gnomad4 FIN AF: 0.449

Gnomad4 NFE AF: 0.486

Gnomad4 OTH AF: 0.423

Alfa AF: 0.436 Hom.: 3072

Bravo AF: 0.378

Asia WGS AF: 0.296 AC: 1031 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.58
Dann	Benign	0.63

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: rs2275703; hg19: chr1-160165095; COSMIC: COSV63624486; COSMIC: COSV63624486;