NM_001042475.3:c.1020+6910C>T

Variant names:

• chr6-118558619-G-A
• rs73526175
• NM_001042475.3:c.1020+6910C>T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Strong BS2_Supporting

The NM_001042475.3(CEP85L):​c.1020+6910C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000129 in 85,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.00013 (0 hom., cov: 25)
• Consequence: CEP85L NM_001042475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.551

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 Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS2: High AC in GnomAd4 at 11 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP85L	NM_001042475.3	c.1020+6910C>T		intron_variant	Intron 3 of 12	ENST00000368491.8	NP_001035940.1
PLN	NM_002667.5	c.-97-206G>A		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+6910C>T		intron_variant	Intron 3 of 12	1	NM_001042475.3	ENSP00000357477.3
PLN	ENST00000357525.6	c.-97-206G>A		intron_variant	Intron 1 of 1	1	NM_002667.5	ENSP00000350132.5

Frequencies

GnomAD3 genomes AF: 0.000129 AC: 11 AN: 85078 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.0000378

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000344

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000323

Gnomad SAS AF: 0.00201

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000536

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.000129 AC: 11 AN: 85174 Hom.: 0 Cov.: 25 AF XY: 0.000123 AC XY: 5 AN XY: 40554

Gnomad4 AFR AF: 0.0000377

Gnomad4 AMR AF: 0.000343

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000323

Gnomad4 SAS AF: 0.00201

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000536

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000100 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.45
DANN	Benign	0.44

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: rs73526175; hg19: chr6-118879782;