chr6-118558656-C-G

Position:

• chr6-118558656-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001042475.3(CEP85L):​c.1020+6873G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 131,888 control chromosomes in the GnomAD database, including 900 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.12 (900 hom., cov: 24)
• Consequence: CEP85L NM_001042475.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.797

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 6-118558656-C-G is Benign according to our data. Variant chr6-118558656-C-G is described in ClinVar as [Benign]. Clinvar id is 1223914.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP85L	NM_001042475.3	c.1020+6873G>C		intron_variant		ENST00000368491.8
PLN	NM_002667.5	c.-97-169C>G		intron_variant		ENST00000357525.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLN	ENST00000357525.6	c.-97-169C>G		intron_variant		1	NM_002667.5	P1
CEP85L	ENST00000368491.8	c.1020+6873G>C		intron_variant		1	NM_001042475.3	P1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 15756 AN: 131806 Hom.: 899 Cov.: 24

Gnomad AFR AF: 0.0636

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.0434

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.141

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.120 AC: 15765 AN: 131888 Hom.: 900 Cov.: 24 AF XY: 0.117 AC XY: 7515 AN XY: 63982

Gnomad4 AFR AF: 0.0638

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.0433

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.127

Alfa AF: 0.127 Hom.: 11

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.40
DANN	Benign	0.30

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

Other links and lift over

dbSNP: rs879231658; hg19: chr6-118879819;