rs77186188

Variant names:

Variant summary

Our verdict is Benign. The variant received -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:5

Conservation

PhyloP100: 1.38

Publications

2 publications found

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 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

PLN links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001042475.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CEP85L	NM_001042475.3	MANE Select	c.1020+17269T>G	intron	N/A	NP_001035940.1	Q5SZL2-1
CEP85L	NM_001178035.2		c.1029+17269T>G	intron	N/A	NP_001171506.1	Q5SZL2-4
CEP85L	NM_206921.3		c.1020+17269T>G	intron	N/A	NP_996804.2	Q5SZL2-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CEP85L	ENST00000368491.8	TSL:1 MANE Select	c.1020+17269T>G	intron	N/A	ENSP00000357477.3	Q5SZL2-1
CEP85L	ENST00000434604.5	TSL:1	c.1029+17269T>G	intron	N/A	ENSP00000392131.1	A2A3P3
CEP85L	ENST00000392500.7	TSL:1	c.1029+17269T>G	intron	N/A	ENSP00000376288.3	Q5SZL2-2

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

African (AFR)

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0833

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0403

AC:

6128

AN:

152102

Hom.:

198

Cov.:

AF XY:

0.0398

AC XY:

2956

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.00910

AC:

378

AN:

41538

American (AMR)

AF:

0.0264

AC:

403

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.0490

AC:

170

AN:

3466

East Asian (EAS)

AF:

0.000386

AC:

AN:

5188

South Asian (SAS)

AF:

0.0160

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0852

AC:

903

AN:

10596

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0600

AC:

4078

AN:

67912

Other (OTH)

AF:

0.0294

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

305

611

916

1222

1527

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

216

288

360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0359

Hom.:

Bravo

AF:

0.0348

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Dilated cardiomyopathy 1P (2)

Lissencephaly 10 (2)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

(source)

DANN

Benign

0.79

PhyloP100

1.4

PromoterAI

-0.010

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over