6-118558626-T-TACAC

Variant summary

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

The NM_001042475.3(CEP85L):c.1020+6902_1020+6903insGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.074 (315 hom., cov: 0)
• Consequence: CEP85L NM_001042475.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.379

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 6-118558626-T-TACAC is Benign according to our data. Variant chr6-118558626-T-TACAC is described in ClinVar as [Benign]. Clinvar id is 1246007.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0989 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP85L	NM_001042475.3	c.1020+6902_1020+6903insGTGT		intron_variant		ENST00000368491.8
PLN	NM_002667.5	c.-97-167_-97-164dup		intron_variant		ENST00000357525.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLN	ENST00000357525.6	c.-97-167_-97-164dup		intron_variant		1	NM_002667.5	P1
CEP85L	ENST00000368491.8	c.1020+6902_1020+6903insGTGT		intron_variant		1	NM_001042475.3	P1

Frequencies

GnomAD3 genomes AF: 0.0744 AC: 8281 AN: 111272 Hom.: 315 Cov.: 0

Gnomad AFR AF: 0.0391

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.0441

Gnomad ASJ AF: 0.0509

Gnomad EAS AF: 0.0570

Gnomad SAS AF: 0.0552

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.0973

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.0668

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

GnomAD4 genome AF: 0.0744 AC: 8279 AN: 111334 Hom.: 315 Cov.: 0 AF XY: 0.0721 AC XY: 3753 AN XY: 52088

Gnomad4 AFR AF: 0.0390

Gnomad4 AMR AF: 0.0441

Gnomad4 ASJ AF: 0.0509

Gnomad4 EAS AF: 0.0570

Gnomad4 SAS AF: 0.0548

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.0661

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 15, 2019

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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: rs371775061; hg19: chr6-118879789;