6-118558646-CACACACACACACACAG-C

Variant names:

• chr6-118558646-CACACACACACACACAG-C
• rs1359281186
• NM_001042475.3:c.1020+6867_1020+6882delCTGTGTGTGTGTGTGT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001042475.3(CEP85L):​c.1020+6867_1020+6882delCTGTGTGTGTGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0228 in 143,290 control chromosomes in the GnomAD database, including 115 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.023 (115 hom., cov: 24)
• Consequence: CEP85L NM_001042475.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.58
• 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: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• intrinsic cardiomyopathy

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

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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 6-118558646-CACACACACACACACAG-C is Benign according to our data. Variant chr6-118558646-CACACACACACACACAG-C is described in ClinVar as Benign. ClinVar VariationId is 1180349.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0811 is higher than 0.05.

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+6867_1020+6882delCTGTGTGTGTGTGTGT		intron	N/A	NP_001035940.1	Q5SZL2-1
	PLN	NM_002667.5	MANE Select	c.-97-177_-97-162delCACACACACACACAGA		intron	N/A	NP_002658.1	P26678
	CEP85L	NM_001178035.2		c.1029+6867_1029+6882delCTGTGTGTGTGTGTGT		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+6867_1020+6882delCTGTGTGTGTGTGTGT		intron	N/A	ENSP00000357477.3	Q5SZL2-1
	PLN	ENST00000357525.6	TSL:1 MANE Select	c.-97-178_-97-163delACACACACACACACAG		intron	N/A	ENSP00000350132.5	P26678
	CEP85L	ENST00000434604.5	TSL:1	c.1029+6867_1029+6882delCTGTGTGTGTGTGTGT		intron	N/A	ENSP00000392131.1	A2A3P3

Frequencies

GnomAD3 genomes AF: 0.0228 AC: 3266 AN: 143166 Hom.: 115 Cov.: 24

Gnomad AFR AF: 0.0836

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00932

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000234

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000365

Gnomad OTH AF: 0.0214

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

GnomAD4 genome AF: 0.0228 AC: 3274 AN: 143290 Hom.: 115 Cov.: 24 AF XY: 0.0214 AC XY: 1493 AN XY: 69800

African (AFR) AF: 0.0835 AC: 3072 AN: 36778

American (AMR) AF: 0.00930 AC: 135 AN: 14512

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3412

East Asian (EAS) AF: 0.00 AC: 0 AN: 5084

South Asian (SAS) AF: 0.000234 AC: 1 AN: 4282

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10254

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.000365 AC: 24 AN: 65792

Other (OTH) AF: 0.0211 AC: 42 AN: 1988

Alfa AF: 0.0197 Hom.: 0

Asia WGS AF: 0.00406 AC: 14 AN: 3464

ClinVar

ClinVar submissions

Significance: 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		1.6
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: rs1359281186; hg19: chr6-118879809;