Variant 5-69167279-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031966.4(CCNB1):c.17C>G(p.Thr6Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000311 in 1,584,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00032 ( 0 hom. )

Consequence

CCNB1
NM_031966.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.89

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07089928).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCNB1	NM_031966.4 linkuse as main transcript	c.17C>G	p.Thr6Ser	missense_variant	1/9	ENST00000256442.10	NP_114172.1	P14635-1
CCNB1	NM_001354844.2 linkuse as main transcript	c.17C>G	p.Thr6Ser	missense_variant	1/8		NP_001341773.1
CCNB1	NM_001354845.2 linkuse as main transcript	c.17C>G	p.Thr6Ser	missense_variant	1/8		NP_001341774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCNB1	ENST00000256442.10 linkuse as main transcript	c.17C>G	p.Thr6Ser	missense_variant	1/9	1	NM_031966.4	ENSP00000256442.5		P14635-1

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000247

AC:

AN:

227004

Hom.:

AF XY:

0.000243

AC XY:

AN XY:

123512

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000671

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000539

Gnomad NFE exome

AF:

0.000495

Gnomad OTH exome

AF:

0.000186

GnomAD4 exome

AF:

0.000321

AC:

460

AN:

1431770

Hom.:

Cov.:

AF XY:

0.000316

AC XY:

225

AN XY:

711514

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000490

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000610

Gnomad4 NFE exome

AF:

0.000402

Gnomad4 OTH exome

AF:

0.000220

GnomAD4 genome

AF:

0.000210

AC:

AN:

152354

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000267

Hom.:

Bravo

AF:

0.000185

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000313

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 28, 2023

The c.17C>G (p.T6S) alteration is located in exon 1 (coding exon 1) of the CCNB1 gene. This alteration results from a C to G substitution at nucleotide position 17, causing the threonine (T) at amino acid position 6 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.45

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.18

T;T;T;.

Eigen

Benign

0.055

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.73

T;T;T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.071

T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.8

L;.;.;L

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-2.0

N;N;N;N

REVEL

Benign

0.076

Sift

Benign

0.098

T;T;T;T

Sift4G

Benign

0.15

T;T;T;T

Polyphen

0.34

B;B;.;.

Vest4

0.13

MutPred

0.42

Gain of phosphorylation at T6 (P = 0.0801);Gain of phosphorylation at T6 (P = 0.0801);Gain of phosphorylation at T6 (P = 0.0801);Gain of phosphorylation at T6 (P = 0.0801);

MVP

0.85

MPC

0.048

ClinPred

0.13

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.24

gMVP

0.49

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over