rs617599

Positions:

• chr1-160193169-G-A
• chr1-160193169-G-C

Variant summary

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

The ENST00000368078.8(CASQ1):​c.364+283G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 152,066 control chromosomes in the GnomAD database, including 8,918 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 0.31 (8918 hom., cov: 32)
• Consequence: CASQ1 ENST00000368078.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASQ1	NM_001231.5	c.364+283G>A		intron_variant		ENST00000368078.8	NP_001222.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASQ1	ENST00000368078.8	c.364+283G>A		intron_variant		1	NM_001231.5	ENSP00000357057	P1
CASQ1	ENST00000481081.1	n.249+283G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46909 AN: 151948 Hom.: 8923 Cov.: 32

Gnomad AFR AF: 0.0860

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.551

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.315

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

GnomAD4 genome AF: 0.308 AC: 46912 AN: 152066 Hom.: 8918 Cov.: 32 AF XY: 0.314 AC XY: 23363 AN XY: 74304

Gnomad4 AFR AF: 0.0858

Gnomad4 AMR AF: 0.392

Gnomad4 ASJ AF: 0.441

Gnomad4 EAS AF: 0.550

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.401

Gnomad4 NFE AF: 0.386

Gnomad4 OTH AF: 0.316

Alfa AF: 0.360 Hom.: 1790

Bravo AF: 0.297

Asia WGS AF: 0.378 AC: 1315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.4
DANN	Benign	0.71

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: rs617599; hg19: chr1-160162959;