chr6-118558624-CAT-C

Variant names:

• chr6-118558624-CAT-C
• rs1349011771
• NM_001042475.3:c.1020+6903_1020+6904delAT

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+6903_1020+6904delAT 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 0.0030 (1 hom., cov: 13)
• Consequence: CEP85L NM_001042475.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.141

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 6-118558624-CAT-C is Benign according to our data. Variant chr6-118558624-CAT-C is described in ClinVar as [Likely_benign]. Clinvar id is 1180239.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00298 (251/84096) while in subpopulation AFR AF= 0.0116 (239/20612). AF 95% confidence interval is 0.0104. There are 1 homozygotes in gnomad4. There are 121 alleles in male gnomad4 subpopulation. Median coverage is 13. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 251 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP85L	NM_001042475.3	c.1020+6903_1020+6904delAT		intron_variant	Intron 3 of 12	ENST00000368491.8	NP_001035940.1
PLN	NM_002667.5	c.-97-199_-97-198delTA		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+6903_1020+6904delAT		intron_variant	Intron 3 of 12	1	NM_001042475.3	ENSP00000357477.3
PLN	ENST00000357525.6	c.-97-200_-97-199delAT		intron_variant	Intron 1 of 1	1	NM_002667.5	ENSP00000350132.5

Frequencies

GnomAD3 genomes AF: 0.00295 AC: 248 AN: 84022 Hom.: 1 Cov.: 13

Gnomad AFR AF: 0.0115

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00141

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000455

Gnomad OTH AF: 0.000977

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

GnomAD4 genome AF: 0.00298 AC: 251 AN: 84096 Hom.: 1 Cov.: 13 AF XY: 0.00307 AC XY: 121 AN XY: 39360

Gnomad4 AFR AF: 0.0116

Gnomad4 AMR AF: 0.00141

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000456

Gnomad4 OTH AF: 0.000963

Alfa AF: 0.000253 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 21, 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

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: rs1349011771; hg19: chr6-118879787;