1-160193169-G-A

Variant names:

• chr1-160193169-G-A
• rs617599
• NM_001231.5:c.364+283G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001231.5(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 NM_001231.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400
• Publications: 9 publications found

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 Gene-Disease associations (from GenCC):

• myopathy due to calsequestrin and SERCA1 protein overload

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• tubular aggregate myopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000304031 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001231.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASQ1	NM_001231.5	MANE Select	c.364+283G>A		intron	N/A	NP_001222.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASQ1	ENST00000368078.8	TSL:1 MANE Select	c.364+283G>A		intron	N/A	ENSP00000357057.3
	CASQ1	ENST00000954562.1		c.364+283G>A		intron	N/A	ENSP00000624621.1
	CASQ1	ENST00000954563.1		c.364+283G>A		intron	N/A	ENSP00000624622.1

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

African (AFR) AF: 0.0858 AC: 3563 AN: 41514

American (AMR) AF: 0.392 AC: 6002 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 1529 AN: 3470

East Asian (EAS) AF: 0.550 AC: 2840 AN: 5162

South Asian (SAS) AF: 0.297 AC: 1431 AN: 4818

European-Finnish (FIN) AF: 0.401 AC: 4232 AN: 10556

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.386 AC: 26222 AN: 67936

Other (OTH) AF: 0.316 AC: 668 AN: 2112

Alfa AF: 0.359 Hom.: 3649

Bravo AF: 0.297

Asia WGS AF: 0.378 AC: 1315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.4
DANN	Benign	0.71
PhyloP100		0.040
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs617599; hg19: chr1-160162959;