Genetic Variant CCNB1:p.Thr330Ser (chr5-69175443-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031966.4(CCNB1):c.989C>G(p.Thr330Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,510 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T330I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CCNB1
NM_031966.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.19

Publications

0 publications found

Variant links:

Genes affected

CCNB1 (HGNC:1579): (cyclin B1) The protein encoded by this gene is a regulatory protein involved in mitosis. The gene product complexes with p34(cdc2) to form the maturation-promoting factor (MPF). The encoded protein is necessary for proper control of the G2/M transition phase of the cell cycle. [provided by RefSeq, Aug 2017]

CCNB1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2294364).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031966.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCNB1	NM_031966.4	MANE Select	c.989C>G	p.Thr330Ser	missense	Exon 7 of 9	NP_114172.1	P14635-1
CCNB1	NM_001354844.2		c.989C>G	p.Thr330Ser	missense	Exon 7 of 8	NP_001341773.1	P14635-2
CCNB1	NM_001354845.2		c.830C>G	p.Thr277Ser	missense	Exon 6 of 8	NP_001341774.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCNB1	ENST00000256442.10	TSL:1 MANE Select	c.989C>G	p.Thr330Ser	missense	Exon 7 of 9	ENSP00000256442.5	P14635-1
CCNB1	ENST00000506572.5	TSL:1	c.989C>G	p.Thr330Ser	missense	Exon 7 of 8	ENSP00000423387.1	E9PC90
CCNB1	ENST00000505500.5	TSL:1	c.989C>G	p.Thr330Ser	missense	Exon 7 of 8	ENSP00000424588.1	P14635-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461510

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727094

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86224

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111708

Other (OTH)

AF:

0.00

AC:

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.29

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.73

M_CAP

Benign

0.0024

MetaRNN

Benign

0.23

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

3.2

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-2.1

REVEL

Benign

0.12

Sift

Benign

0.21

Sift4G

Benign

0.39

Polyphen

0.0010

Vest4

0.13

MutPred

0.70

Gain of phosphorylation at Y334 (P = 0.1915)

MVP

0.84

MPC

0.048

ClinPred

0.21

GERP RS

6.2

Varity_R

0.21

gMVP

0.37

Mutation Taster

=79/21

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over