5-55232560-G-C

Variant names:

• chr5-55232560-G-C
• rs72749883
• NM_021147.5:c.382-14C>G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_021147.5(CCNO):​c.382-14C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0799 in 1,612,396 control chromosomes in the GnomAD database, including 5,723 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.065 (389 hom., cov: 33)
  • Exomes 𝑓: 0.082 (5334 hom.)
• Consequence: CCNO NM_021147.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.780

Genes affected

CCNO (HGNC:18576): (cyclin O) This gene encodes a member of the cyclin protein family, and the encoded protein is involved in regulation of the cell cycle. Disruption of this gene is associated with primary ciliary dyskinesia-19. Alternative splicing results in multiple transcript variants. This gene, which has a previous symbol of UNG2, was erroneously identified as a uracil DNA glycosylase in PubMed ID: 2001396. A later publication, PubMed ID: 8419333, identified this gene's product as a cyclin protein family member. The UNG2 symbol is also used as a specific protein isoform name for the UNG gene (GeneID 7374), so confusion exists in the scientific literature and in some databases for these two genes. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 5-55232560-G-C is Benign according to our data. Variant chr5-55232560-G-C is described in ClinVar as [Benign]. Clinvar id is 402509.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-55232560-G-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0849 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCNO	NM_021147.5	c.382-14C>G		intron_variant	Intron 1 of 2	ENST00000282572.5	NP_066970.3
CCNO	NR_125348.1	n.432C>G		non_coding_transcript_exon_variant	Exon 1 of 2
CCNO	NR_125346.2	n.843-14C>G		intron_variant	Intron 1 of 2
CCNO	NR_125347.2	n.472-14C>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCNO	ENST00000282572.5	c.382-14C>G		intron_variant	Intron 1 of 2	1	NM_021147.5	ENSP00000282572.4
CCNO	ENST00000501463.2	n.*362-14C>G		intron_variant	Intron 1 of 2	1		ENSP00000422485.1

Frequencies

GnomAD3 genomes AF: 0.0647 AC: 9852 AN: 152216 Hom.: 389 Cov.: 33

Gnomad AFR AF: 0.0325

Gnomad AMI AF: 0.0945

Gnomad AMR AF: 0.0659

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0532

Gnomad FIN AF: 0.0651

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0868

Gnomad OTH AF: 0.0794

GnomAD3 exomes AF: 0.0645 AC: 15861 AN: 246032 Hom.: 599 AF XY: 0.0664 AC XY: 8897 AN XY: 134056

Gnomad AFR exome AF: 0.0324

Gnomad AMR exome AF: 0.0457

Gnomad ASJ exome AF: 0.0985

Gnomad EAS exome AF: 0.000381

Gnomad SAS exome AF: 0.0549

Gnomad FIN exome AF: 0.0598

Gnomad NFE exome AF: 0.0854

Gnomad OTH exome AF: 0.0781

GnomAD4 exome AF: 0.0815 AC: 119039 AN: 1460062 Hom.: 5334 Cov.: 32 AF XY: 0.0809 AC XY: 58749 AN XY: 726332

Gnomad4 AFR exome AF: 0.0300

Gnomad4 AMR exome AF: 0.0479

Gnomad4 ASJ exome AF: 0.0980

Gnomad4 EAS exome AF: 0.000227

Gnomad4 SAS exome AF: 0.0560

Gnomad4 FIN exome AF: 0.0574

Gnomad4 NFE exome AF: 0.0899

Gnomad4 OTH exome AF: 0.0841

GnomAD4 genome AF: 0.0647 AC: 9853 AN: 152334 Hom.: 389 Cov.: 33 AF XY: 0.0637 AC XY: 4741 AN XY: 74480

Gnomad4 AFR AF: 0.0326

Gnomad4 AMR AF: 0.0658

Gnomad4 ASJ AF: 0.104

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0528

Gnomad4 FIN AF: 0.0651

Gnomad4 NFE AF: 0.0868

Gnomad4 OTH AF: 0.0781

Alfa AF: 0.0466 Hom.: 60

Bravo AF: 0.0638

Asia WGS AF: 0.0250 AC: 86 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Primary ciliary dyskinesia Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	12
DANN	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs72749883; hg19: chr5-54528388;