rs3747623

Positions:

• chr1-160193719-C-T

Variant summary

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

The NM_001231.5(CASQ1):​c.365-28C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 1,292,934 control chromosomes in the GnomAD database, including 90,849 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.31 (8667 hom., cov: 32)
  • Exomes 𝑓: 0.37 (82182 hom.)
• Consequence: CASQ1 NM_001231.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28

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]

CASQ1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: This place is a probable branch point but likely benign (scored 2 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASQ1	NM_001231.5	c.365-28C>T		intron_variant		ENST00000368078.8	NP_001222.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASQ1	ENST00000368078.8	c.365-28C>T		intron_variant		1	NM_001231.5	ENSP00000357057.3
CASQ1	ENST00000481081.1	n.250-28C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46743 AN: 151186 Hom.: 8672 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.315

GnomAD3 exomes AF: 0.372 AC: 85948 AN: 230924 Hom.: 17138 AF XY: 0.371 AC XY: 46648 AN XY: 125612

Gnomad AFR exome AF: 0.0928

Gnomad AMR exome AF: 0.414

Gnomad ASJ exome AF: 0.440

Gnomad EAS exome AF: 0.558

Gnomad SAS exome AF: 0.298

Gnomad FIN exome AF: 0.399

Gnomad NFE exome AF: 0.380

Gnomad OTH exome AF: 0.380

GnomAD4 exome AF: 0.373 AC: 426299 AN: 1141628 Hom.: 82182 Cov.: 15 AF XY: 0.372 AC XY: 215240 AN XY: 578926

Gnomad4 AFR exome AF: 0.0887

Gnomad4 AMR exome AF: 0.406

Gnomad4 ASJ exome AF: 0.438

Gnomad4 EAS exome AF: 0.543

Gnomad4 SAS exome AF: 0.303

Gnomad4 FIN exome AF: 0.413

Gnomad4 NFE exome AF: 0.376

Gnomad4 OTH exome AF: 0.371

GnomAD4 genome AF: 0.309 AC: 46751 AN: 151306 Hom.: 8667 Cov.: 32 AF XY: 0.314 AC XY: 23251 AN XY: 73942

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.380

Gnomad4 ASJ AF: 0.438

Gnomad4 EAS AF: 0.557

Gnomad4 SAS AF: 0.296

Gnomad4 FIN AF: 0.395

Gnomad4 NFE AF: 0.382

Gnomad4 OTH AF: 0.316

Alfa AF: 0.368 Hom.: 17523

Bravo AF: 0.296

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.3
DANN	Benign	0.51
BranchPoint Hunter		2.0

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: rs3747623; hg19: chr1-160163509; COSMIC: COSV63623890; COSMIC: COSV63623890;