rs77186188

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001042475.3(CEP85L):c.1020+17269T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0403 in 152,116 control chromosomes in the GnomAD database, including 198 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.040 ( 198 hom., cov: 32)

Exomes 𝑓: 0.071 ( 0 hom. )

Consequence

CEP85L
NM_001042475.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts P:1B:4

Conservation

PhyloP100: 1.38

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 6-118548260-A-C is Benign according to our data. Variant chr6-118548260-A-C is described in ClinVar as [Benign]. Clinvar id is 403328.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP85L	NM_001042475.3 link	c.1020+17269T>G		intron_variant	Intron 3 of 12	ENST00000368491.8	NP_001035940.1	Q5SZL2-1Q3ZCQ5
PLN	NM_002667.5 link	c.-230A>C		upstream_gene_variant		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+17269T>G		intron_variant	Intron 3 of 12	1	NM_001042475.3	ENSP00000357477.3		Q5SZL2-1
PLN	ENST00000357525.6 link	c.-230A>C		upstream_gene_variant		1	NM_002667.5	ENSP00000350132.5		P26678

Frequencies

GnomAD3 genomes

AF:

0.0403

AC:

6130

AN:

151984

Hom.:

199

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00913

Gnomad AMI

AF:

0.0582

Gnomad AMR

AF:

0.0264

Gnomad ASJ

AF:

0.0490

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0160

Gnomad FIN

AF:

0.0852

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0601

Gnomad OTH

AF:

0.0298

GnomAD4 exome

AF:

0.0714

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0833

AC XY:

AN XY:

show subpopulations

Gnomad4 AMR exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0833

GnomAD4 genome

AF:

0.0403

AC:

6128

AN:

152102

Hom.:

198

Cov.:

AF XY:

0.0398

AC XY:

2956

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00910

Gnomad4 AMR

AF:

0.0264

Gnomad4 ASJ

AF:

0.0490

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0160

Gnomad4 FIN

AF:

0.0852

Gnomad4 NFE

AF:

0.0600

Gnomad4 OTH

AF:

0.0294

Alfa

AF:

0.0490

Hom.:

Bravo

AF:

0.0348

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Dilated cardiomyopathy 1P

Pathogenic:1Benign:1

Pathogenic, no assertion criteria provided	literature only	OMIM	May 01, 2008	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 27, 2025	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in 1000Genomes: 67/2178=3% -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

This variant is associated with the following publications: (PMID: 18241046, 24037902, 21167350) -

Lissencephaly 10

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Nov 02, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Benign

0.79

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