Genetic Variant CEP85L:c.1020+6865C>G (chr6-118558664-G-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001042475.3(CEP85L):c.1020+6865C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.36 ( 7386 hom., cov: 19)

Consequence

CEP85L
NM_001042475.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.46

Variant links:

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]

CEP85L links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 6-118558664-G-C is Benign according to our data. Variant chr6-118558664-G-C is described in ClinVar as [Benign]. Clinvar id is 1225868.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP85L	NM_001042475.3 link	c.1020+6865C>G		intron_variant	Intron 3 of 12	ENST00000368491.8	NP_001035940.1	Q5SZL2-1Q3ZCQ5
PLN	NM_002667.5 link	c.-97-161G>C		intron_variant	Intron 1 of 1	ENST00000357525.6	NP_002658.1	P26678Q5R352

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP85L	ENST00000368491.8 link	c.1020+6865C>G		intron_variant	Intron 3 of 12	1	NM_001042475.3	ENSP00000357477.3		Q5SZL2-1
PLN	ENST00000357525.6 link	c.-97-161G>C		intron_variant	Intron 1 of 1	1	NM_002667.5	ENSP00000350132.5		P26678

Frequencies

GnomAD3 genomes

AF:

0.364

AC:

43889

AN:

120462

Hom.:

7395

Cov.:

show subpopulations

Gnomad AFR

AF:

0.285

Gnomad AMI

AF:

0.373

Gnomad AMR

AF:

0.272

Gnomad ASJ

AF:

0.367

Gnomad EAS

AF:

0.260

Gnomad SAS

AF:

0.376

Gnomad FIN

AF:

0.356

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.443

Gnomad OTH

AF:

0.350

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

GnomAD4 genome

AF:

0.364

AC:

43883

AN:

120542

Hom.:

7386

Cov.:

AF XY:

0.354

AC XY:

20391

AN XY:

57576

show subpopulations

Gnomad4 AFR

AF:

0.285

Gnomad4 AMR

AF:

0.271

Gnomad4 ASJ

AF:

0.367

Gnomad4 EAS

AF:

0.260

Gnomad4 SAS

AF:

0.374

Gnomad4 FIN

AF:

0.356

Gnomad4 NFE

AF:

0.443

Gnomad4 OTH

AF:

0.350

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 18, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.77

DANN

Benign

0.23

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over