6-118558658-CACAGAG-C

Variant names:

• chr6-118558658-CACAGAG-C
• rs1314630868
• NM_001042475.3:c.1020+6865_1020+6870delCTCTGT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001042475.3(CEP85L):​c.1020+6865_1020+6870delCTCTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0097 (4 hom., cov: 17)
• Consequence: CEP85L NM_001042475.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.43

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 6-118558658-CACAGAG-C is Benign according to our data. Variant chr6-118558658-CACAGAG-C is described in ClinVar as [Likely_benign]. Clinvar id is 1196240.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00972 (1214/124924) while in subpopulation NFE AF= 0.0154 (928/60372). AF 95% confidence interval is 0.0146. There are 4 homozygotes in gnomad4. There are 517 alleles in male gnomad4 subpopulation. Median coverage is 17. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1214 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP85L	NM_001042475.3	c.1020+6865_1020+6870delCTCTGT		intron_variant	Intron 3 of 12	ENST00000368491.8	NP_001035940.1
PLN	NM_002667.5	c.-97-165_-97-160delCAGAGA		intron_variant	Intron 1 of 1	ENST00000357525.6	NP_002658.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP85L	ENST00000368491.8	c.1020+6865_1020+6870delCTCTGT		intron_variant	Intron 3 of 12	1	NM_001042475.3	ENSP00000357477.3
PLN	ENST00000357525.6	c.-97-166_-97-161delACAGAG		intron_variant	Intron 1 of 1	1	NM_002667.5	ENSP00000350132.5

Frequencies

GnomAD3 genomes AF: 0.00972 AC: 1213 AN: 124850 Hom.: 4 Cov.: 17

Gnomad AFR AF: 0.00319

Gnomad AMI AF: 0.00950

Gnomad AMR AF: 0.00671

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.000467

Gnomad SAS AF: 0.00168

Gnomad FIN AF: 0.00552

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0154

Gnomad OTH AF: 0.00514

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

GnomAD4 genome AF: 0.00972 AC: 1214 AN: 124924 Hom.: 4 Cov.: 17 AF XY: 0.00857 AC XY: 517 AN XY: 60352

Gnomad4 AFR AF: 0.00318

Gnomad4 AMR AF: 0.00671

Gnomad4 ASJ AF: 0.0112

Gnomad4 EAS AF: 0.000468

Gnomad4 SAS AF: 0.00168

Gnomad4 FIN AF: 0.00552

Gnomad4 NFE AF: 0.0154

Gnomad4 OTH AF: 0.00566

Alfa AF: 0.0108 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 13, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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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: rs1314630868; hg19: chr6-118879821;