rs3838216

Variant names:

• chr1-160191838-T-TGGCCTGGCATTCAGATA
• rs3838216
• NM_001231.5:c.279+813_279+814insGGCATTCAGATAGGCCT

Your query was ambiguous. Multiple possible variants found:

• chr1-160191838-T-TGGCCTGGCATTCAGATA
• chr1-160191838-T-TGGCCTGGCATTCAGATC
• chr1-160191838-T-TGGCCTGGCATTCAGGTA

Variant summary

Our verdict is Benign. The variant received -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. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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
• Publications: 3 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: Orphanet, Labcorp Genetics (formerly Invitae)
• tubular aggregate myopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000304031 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.56 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASQ1	NM_001231.5	MANE Select	c.279+813_279+814insGGCATTCAGATAGGCCT		intron	N/A	NP_001222.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASQ1	ENST00000368078.8	TSL:1 MANE Select	c.279+808_279+809insGGCCTGGCATTCAGATA		intron	N/A	ENSP00000357057.3	P31415
	CASQ1	ENST00000954562.1		c.279+808_279+809insGGCCTGGCATTCAGATA		intron	N/A	ENSP00000624621.1
	CASQ1	ENST00000954563.1		c.279+808_279+809insGGCCTGGCATTCAGATA		intron	N/A	ENSP00000624622.1

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

African (AFR) AF: 0.566 AC: 23477 AN: 41478

American (AMR) AF: 0.226 AC: 3463 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 657 AN: 3472

East Asian (EAS) AF: 0.128 AC: 665 AN: 5182

South Asian (SAS) AF: 0.335 AC: 1610 AN: 4804

European-Finnish (FIN) AF: 0.193 AC: 2046 AN: 10610

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.234 AC: 15910 AN: 68002

Other (OTH) AF: 0.294 AC: 620 AN: 2112

Alfa AF: 0.105 Hom.: 123

Asia WGS AF: 0.281 AC: 978 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3838216; hg19: chr1-160161628; COSMIC: COSV63624153; COSMIC: COSV63624153;