chr6-118558626-T-TACACACAC

Variant names:

• chr6-118558626-T-TACACACAC
• rs371775061
• NM_001042475.3:c.1020+6895_1020+6902dupGTGTGTGT

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+6895_1020+6902dupGTGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.048 (127 hom., cov: 0)
• Consequence: CEP85L NM_001042475.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.379
• 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 6-118558626-T-TACACACAC is Benign according to our data. Variant chr6-118558626-T-TACACACAC is described in ClinVar as Benign. ClinVar VariationId is 1236113.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0717 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+6895_1020+6902dupGTGTGTGT		intron	N/A	NP_001035940.1	Q5SZL2-1
	PLN	NM_002667.5	MANE Select	c.-97-171_-97-164dupCACACACA		intron	N/A	NP_002658.1	P26678
	CEP85L	NM_001178035.2		c.1029+6895_1029+6902dupGTGTGTGT		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+6902_1020+6903insGTGTGTGT		intron	N/A	ENSP00000357477.3	Q5SZL2-1
	PLN	ENST00000357525.6	TSL:1 MANE Select	c.-97-199_-97-198insACACACAC		intron	N/A	ENSP00000350132.5	P26678
	CEP85L	ENST00000434604.5	TSL:1	c.1029+6902_1029+6903insGTGTGTGT		intron	N/A	ENSP00000392131.1	A2A3P3

Frequencies

GnomAD3 genomes AF: 0.0479 AC: 5330 AN: 111182 Hom.: 128 Cov.: 0

Gnomad AFR AF: 0.0325

Gnomad AMI AF: 0.0623

Gnomad AMR AF: 0.0349

Gnomad ASJ AF: 0.0734

Gnomad EAS AF: 0.0303

Gnomad SAS AF: 0.0816

Gnomad FIN AF: 0.0264

Gnomad MID AF: 0.0752

Gnomad NFE AF: 0.0594

Gnomad OTH AF: 0.0557

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

GnomAD4 genome AF: 0.0479 AC: 5327 AN: 111244 Hom.: 127 Cov.: 0 AF XY: 0.0463 AC XY: 2412 AN XY: 52058

African (AFR) AF: 0.0324 AC: 996 AN: 30752

American (AMR) AF: 0.0347 AC: 386 AN: 11116

Ashkenazi Jewish (ASJ) AF: 0.0734 AC: 210 AN: 2860

East Asian (EAS) AF: 0.0301 AC: 120 AN: 3984

South Asian (SAS) AF: 0.0806 AC: 210 AN: 2606

European-Finnish (FIN) AF: 0.0264 AC: 126 AN: 4764

Middle Eastern (MID) AF: 0.0769 AC: 16 AN: 208

European-Non Finnish (NFE) AF: 0.0594 AC: 3132 AN: 52726

Other (OTH) AF: 0.0570 AC: 85 AN: 1490

Alfa AF: 0.0507 Hom.: 143

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		0.38
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: rs371775061; hg19: chr6-118879789;