rs1314630868

Variant names:

• chr6-118558658-CACAGAG-C
• rs1314630868
• NM_001042475.3:c.1020+6865_1020+6870delCTCTGT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001042475.3(CEP85L):​c.1020+6865_1020+6870delCTCTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0097 (4 hom., cov: 17)
• Consequence: CEP85L NM_001042475.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.43
• Publications: 0 publications found

Genes affected

CEP85L (HGNC:21638): (centrosomal protein 85 like) The protein encoded by this gene was identified as a breast cancer antigen. Nothing more is known of its function at this time. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2010]

PLN (HGNC:9080): (phospholamban) The protein encoded by this gene is found as a pentamer and is a major substrate for the cAMP-dependent protein kinase in cardiac muscle. The encoded protein is an inhibitor of cardiac muscle sarcoplasmic reticulum Ca(2+)-ATPase in the unphosphorylated state, but inhibition is relieved upon phosphorylation of the protein. The subsequent activation of the Ca(2+) pump leads to enhanced muscle relaxation rates, thereby contributing to the inotropic response elicited in heart by beta-agonists. The encoded protein is a key regulator of cardiac diastolic function. Mutations in this gene are a cause of inherited human dilated cardiomyopathy with refractory congestive heart failure, and also familial hypertrophic cardiomyopathy. [provided by RefSeq, Apr 2016]

PLN Gene-Disease associations (from GenCC):

• dilated cardiomyopathy 1P

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• intrinsic cardiomyopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• hypertrophic cardiomyopathy 18

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
• arrhythmogenic right ventricular cardiomyopathy

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 6-118558658-CACAGAG-C is Benign according to our data. Variant chr6-118558658-CACAGAG-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1196240.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00972 (1214/124924) while in subpopulation NFE AF = 0.0154 (928/60372). AF 95% confidence interval is 0.0146. There are 4 homozygotes in GnomAd4. There are 517 alleles in the male GnomAd4 subpopulation. Median coverage is 17. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1214 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042475.3. 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
	CEP85L	NM_001042475.3	MANE Select	c.1020+6865_1020+6870delCTCTGT		intron	N/A	NP_001035940.1	Q5SZL2-1
	PLN	NM_002667.5	MANE Select	c.-97-165_-97-160delCAGAGA		intron	N/A	NP_002658.1	P26678
	CEP85L	NM_001178035.2		c.1029+6865_1029+6870delCTCTGT		intron	N/A	NP_001171506.1	Q5SZL2-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP85L	ENST00000368491.8	TSL:1 MANE Select	c.1020+6865_1020+6870delCTCTGT		intron	N/A	ENSP00000357477.3	Q5SZL2-1
	PLN	ENST00000357525.6	TSL:1 MANE Select	c.-97-166_-97-161delACAGAG		intron	N/A	ENSP00000350132.5	P26678
	CEP85L	ENST00000434604.5	TSL:1	c.1029+6865_1029+6870delCTCTGT		intron	N/A	ENSP00000392131.1	A2A3P3

Frequencies

GnomAD3 genomes AF: 0.00972 AC: 1213 AN: 124850 Hom.: 4 Cov.: 17

Gnomad AFR AF: 0.00319

Gnomad AMI AF: 0.00950

Gnomad AMR AF: 0.00671

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.000467

Gnomad SAS AF: 0.00168

Gnomad FIN AF: 0.00552

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0154

Gnomad OTH AF: 0.00514

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

GnomAD4 genome AF: 0.00972 AC: 1214 AN: 124924 Hom.: 4 Cov.: 17 AF XY: 0.00857 AC XY: 517 AN XY: 60352

African (AFR) AF: 0.00318 AC: 95 AN: 29896

American (AMR) AF: 0.00671 AC: 82 AN: 12220

Ashkenazi Jewish (ASJ) AF: 0.0112 AC: 36 AN: 3204

East Asian (EAS) AF: 0.000468 AC: 2 AN: 4272

South Asian (SAS) AF: 0.00168 AC: 6 AN: 3580

European-Finnish (FIN) AF: 0.00552 AC: 47 AN: 8514

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 256

European-Non Finnish (NFE) AF: 0.0154 AC: 928 AN: 60372

Other (OTH) AF: 0.00566 AC: 10 AN: 1768

Alfa AF: 0.0108 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs1314630868; hg19: chr6-118879821;