dbSNP rs139167004: CCNO:p.Ala260Ala (chr5-55231648-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_021147.5(CCNO):c.780C>T(p.Ala260Ala) 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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.137

Publications

2 publications found

Variant links:

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]

CCNO Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 29
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Ambry Genetics
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CCNO links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021147.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCNO	NM_021147.5	MANE Select	c.780C>T	p.Ala260Ala	synonymous	Exon 3 of 3	NP_066970.3	P22674-1
CCNO	NR_125346.2		n.1241C>T		non_coding_transcript_exon	Exon 3 of 3
CCNO	NR_125347.2		n.870C>T		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCNO	ENST00000282572.5	TSL:1 MANE Select	c.780C>T	p.Ala260Ala	synonymous	Exon 3 of 3	ENSP00000282572.4	P22674-1
CCNO	ENST00000501463.2	TSL:1	n.*760C>T		non_coding_transcript_exon	Exon 3 of 3	ENSP00000422485.1	P22674-2
CCNO	ENST00000501463.2	TSL:1	n.*760C>T		3_prime_UTR	Exon 3 of 3	ENSP00000422485.1	P22674-2

Frequencies

GnomAD3 genomes

AF:

0.00353

AC:

538

AN:

152228

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.00451

AC:

893

AN:

198212

AF XY:

0.00484

show subpopulations

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 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.:

Cov.:

AF XY:

0.00478

AC XY:

3404

AN XY:

712596

show subpopulations

African (AFR)

AF:

0.00161

AC:

AN:

32956

American (AMR)

AF:

0.00606

AC:

244

AN:

40246

Ashkenazi Jewish (ASJ)

AF:

0.00367

AC:

AN:

25634

East Asian (EAS)

AF:

0.00

AC:

AN:

38258

South Asian (SAS)

AF:

0.00743

AC:

623

AN:

83802

European-Finnish (FIN)

AF:

0.00143

AC:

AN:

50342

Middle Eastern (MID)

AF:

0.0282

AC:

161

AN:

5706

European-Non Finnish (NFE)

AF:

0.00450

AC:

4949

AN:

1099844

Other (OTH)

AF:

0.00579

AC:

344

AN:

59368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

443

887

1330

1774

2217

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

184

368

552

736

920

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00352

AC:

536

AN:

152346

Hom.:

Cov.:

AF XY:

0.00346

AC XY:

258

AN XY:

74518

show subpopulations

African (AFR)

AF:

0.00101

AC:

AN:

41588

American (AMR)

AF:

0.00340

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00346

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00621

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00113

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00494

AC:

336

AN:

68026

Other (OTH)

AF:

0.00709

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

117

146

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00417

Hom.:

Bravo

AF:

0.00357

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

7.0

(source)

DANN

Benign

0.84

PhyloP100

-0.14

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over