1-160193082-A-G

Variant names:

• chr1-160193082-A-G
• rs617698
• NM_001231.5:c.364+196A>G

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+196A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 151,940 control chromosomes in the GnomAD database, including 9,488 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 0.33 (9488 hom., cov: 32)
• Consequence: CASQ1 NM_001231.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.434
• Publications: 32 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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASQ1	NM_001231.5	c.364+196A>G		intron_variant	Intron 2 of 10	ENST00000368078.8	NP_001222.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASQ1	ENST00000368078.8	c.364+196A>G		intron_variant	Intron 2 of 10	1	NM_001231.5	ENSP00000357057.3

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50237 AN: 151822 Hom.: 9493 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.331 AC: 50245 AN: 151940 Hom.: 9488 Cov.: 32 AF XY: 0.336 AC XY: 24949 AN XY: 74236

African (AFR) AF: 0.149 AC: 6169 AN: 41426

American (AMR) AF: 0.406 AC: 6197 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 1587 AN: 3472

East Asian (EAS) AF: 0.558 AC: 2880 AN: 5160

South Asian (SAS) AF: 0.302 AC: 1454 AN: 4812

European-Finnish (FIN) AF: 0.401 AC: 4228 AN: 10552

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.392 AC: 26594 AN: 67924

Other (OTH) AF: 0.334 AC: 704 AN: 2110

Alfa AF: 0.367 Hom.: 18317

Bravo AF: 0.321

Asia WGS AF: 0.387 AC: 1346 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.9
DANN	Benign	0.86
PhyloP100		0.43
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: rs617698; hg19: chr1-160162872;