rs3838216

chr1-160191838-T-TGGCCTGGCATTCAGATAchr1-160191838-T-TGGCCTGGCATTCAGATCchr1-160191838-T-TGGCCTGGCATTCAGGTA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001231.5(CASQ1):c.279+813_279+814insGGCATTCAGATAGGCCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 152,156 control chromosomes in the GnomAD database, including 9,618 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.32 (9618 hom., cov: 0)
• Consequence: CASQ1 NM_001231.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASQ1	NM_001231.5	c.279+813_279+814insGGCATTCAGATAGGCCT		intron_variant		ENST00000368078.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASQ1	ENST00000368078.8	c.279+813_279+814insGGCATTCAGATAGGCCT		intron_variant		1	NM_001231.5	P1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48594 AN: 152036 Hom.: 9589 Cov.: 0

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.287

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.295

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

GnomAD4 genome AF: 0.320 AC: 48662 AN: 152156 Hom.: 9618 Cov.: 0 AF XY: 0.315 AC XY: 23456 AN XY: 74398

Gnomad4 AFR AF: 0.566

Gnomad4 AMR AF: 0.226

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.128

Gnomad4 SAS AF: 0.335

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.294

Alfa AF: 0.105 Hom.: 123

Asia WGS AF: 0.281 AC: 978 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3838216; hg19: chr1-160161628;