6-118558646-CACACACACACACACAG-C

Position:

• chr6-118558646-CACACACACACACACAG-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001042475.3(CEP85L):​c.1020+6867_1020+6882del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0228 in 143,290 control chromosomes in the GnomAD database, including 115 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.023 (115 hom., cov: 24)
• Consequence: CEP85L NM_001042475.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.58

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 -10 ACMG points.

• BP6: Variant 6-118558646-CACACACACACACACAG-C is Benign according to our data. Variant chr6-118558646-CACACACACACACACAG-C is described in ClinVar as [Benign]. Clinvar id is 1180349.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP85L	NM_001042475.3	c.1020+6867_1020+6882del		intron_variant		ENST00000368491.8	NP_001035940.1
PLN	NM_002667.5	c.-97-177_-97-162del		intron_variant		ENST00000357525.6	NP_002658.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLN	ENST00000357525.6	c.-97-177_-97-162del		intron_variant		1	NM_002667.5	ENSP00000350132	P1
CEP85L	ENST00000368491.8	c.1020+6867_1020+6882del		intron_variant		1	NM_001042475.3	ENSP00000357477	P1

Frequencies

GnomAD3 genomes AF: 0.0228 AC: 3266 AN: 143166 Hom.: 115 Cov.: 24

Gnomad AFR AF: 0.0836

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00932

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000234

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000365

Gnomad OTH AF: 0.0214

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

GnomAD4 genome AF: 0.0228 AC: 3274 AN: 143290 Hom.: 115 Cov.: 24 AF XY: 0.0214 AC XY: 1493 AN XY: 69800

Gnomad4 AFR AF: 0.0835

Gnomad4 AMR AF: 0.00930

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000234

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000365

Gnomad4 OTH AF: 0.0211

Alfa AF: 0.0197 Hom.: 0

Asia WGS AF: 0.00406 AC: 14 AN: 3464

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 13, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1359281186; hg19: chr6-118879809;