rs139167004

Positions:

• chr5-55231648-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_021147.5(CCNO):​c.780C>T​(p.Ala260=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00445 in 1,588,502 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0035 (5 hom., cov: 33)
  • Exomes 𝑓: 0.0046 (31 hom.)
• Consequence: CCNO NM_021147.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.137

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 5-55231648-G-A is Benign according to our data. Variant chr5-55231648-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 241374.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.137 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00352 (536/152346) while in subpopulation SAS AF= 0.00621 (30/4832). AF 95% confidence interval is 0.0045. There are 5 homozygotes in gnomad4. There are 258 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCNO	NM_021147.5	c.780C>T	p.Ala260=	synonymous_variant	3/3	ENST00000282572.5	NP_066970.3
CCNO	NR_125346.2	n.1241C>T		non_coding_transcript_exon_variant	3/3
CCNO	NR_125347.2	n.870C>T		non_coding_transcript_exon_variant	3/3
CCNO	NR_125348.1	n.844C>T		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCNO	ENST00000282572.5	c.780C>T	p.Ala260=	synonymous_variant	3/3	1	NM_021147.5	ENSP00000282572	P1
CCNO	ENST00000501463.2	c.*760C>T		3_prime_UTR_variant, NMD_transcript_variant	3/3	1		ENSP00000422485

Frequencies

GnomAD3 genomes AF: 0.00353 AC: 538 AN: 152228 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.00101

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.00340

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00620

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.00495

Gnomad OTH AF: 0.00716

GnomAD3 exomes AF: 0.00451 AC: 893 AN: 198212 Hom.: 4 AF XY: 0.00484 AC XY: 521 AN XY: 107592

Gnomad AFR exome AF: 0.000854

Gnomad AMR exome AF: 0.00582

Gnomad ASJ exome AF: 0.00399

Gnomad EAS exome AF: 0.0000684

Gnomad SAS exome AF: 0.00683

Gnomad FIN exome AF: 0.00129

Gnomad NFE exome AF: 0.00515

Gnomad OTH exome AF: 0.00737

GnomAD4 exome AF: 0.00455 AC: 6540 AN: 1436156 Hom.: 31 Cov.: 31 AF XY: 0.00478 AC XY: 3404 AN XY: 712596

Gnomad4 AFR exome AF: 0.00161

Gnomad4 AMR exome AF: 0.00606

Gnomad4 ASJ exome AF: 0.00367

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00743

Gnomad4 FIN exome AF: 0.00143

Gnomad4 NFE exome AF: 0.00450

Gnomad4 OTH exome AF: 0.00579

GnomAD4 genome AF: 0.00352 AC: 536 AN: 152346 Hom.: 5 Cov.: 33 AF XY: 0.00346 AC XY: 258 AN XY: 74518

Gnomad4 AFR AF: 0.00101

Gnomad4 AMR AF: 0.00340

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00621

Gnomad4 FIN AF: 0.00113

Gnomad4 NFE AF: 0.00494

Gnomad4 OTH AF: 0.00709

Alfa AF: 0.00417 Hom.: 1

Bravo AF: 0.00357

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 20, 2021	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	CCNO: BP4, BP7, BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Primary ciliary dyskinesia Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.0
DANN	Benign	0.84

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: rs139167004; hg19: chr5-54527476;