rs822450

Positions:

• chr1-160198578-G-A
• chr1-160198578-G-C

Variant summary

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

The NM_001231.5(CASQ1):​c.829-99G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 812,808 control chromosomes in the GnomAD database, including 70,132 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 0.35 (10756 hom., cov: 31)
  • Exomes 𝑓: 0.42 (59376 hom.)
• Consequence: CASQ1 NM_001231.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASQ1	NM_001231.5	c.829-99G>A		intron_variant		ENST00000368078.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASQ1	ENST00000368078.8	c.829-99G>A		intron_variant		1	NM_001231.5	P1
CASQ1	ENST00000467691.1	c.-9-99G>A		intron_variant		3
CASQ1	ENST00000481081.1	n.714-99G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53164 AN: 151884 Hom.: 10760 Cov.: 31

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.358

GnomAD4 exome AF: 0.416 AC: 274659 AN: 660804 Hom.: 59376 AF XY: 0.411 AC XY: 142133 AN XY: 346136

Gnomad4 AFR exome AF: 0.133

Gnomad4 AMR exome AF: 0.426

Gnomad4 ASJ exome AF: 0.475

Gnomad4 EAS exome AF: 0.517

Gnomad4 SAS exome AF: 0.290

Gnomad4 FIN exome AF: 0.467

Gnomad4 NFE exome AF: 0.427

Gnomad4 OTH exome AF: 0.411

GnomAD4 genome AF: 0.350 AC: 53171 AN: 152004 Hom.: 10756 Cov.: 31 AF XY: 0.353 AC XY: 26255 AN XY: 74292

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.421

Gnomad4 ASJ AF: 0.483

Gnomad4 EAS AF: 0.530

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.442

Gnomad4 NFE AF: 0.434

Gnomad4 OTH AF: 0.358

Alfa AF: 0.307 Hom.: 1213

Bravo AF: 0.339

Asia WGS AF: 0.366 AC: 1273 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	9.4
DANN	Benign	0.51

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: rs822450; hg19: chr1-160168368;