Variant 5-69168072-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_031966.4(CCNB1):c.186G>T(p.Met62Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000392 in 1,613,524 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00039 ( 1 hom. )

Consequence

CCNB1
NM_031966.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.722

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.023091882).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCNB1	NM_031966.4 linkuse as main transcript	c.186G>T	p.Met62Ile	missense_variant	2/9	ENST00000256442.10	NP_114172.1	P14635-1
CCNB1	NM_001354844.2 linkuse as main transcript	c.186G>T	p.Met62Ile	missense_variant	2/8		NP_001341773.1
CCNB1	NM_001354845.2 linkuse as main transcript	c.186G>T	p.Met62Ile	missense_variant	2/8		NP_001341774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCNB1	ENST00000256442.10 linkuse as main transcript	c.186G>T	p.Met62Ile	missense_variant	2/9	1	NM_031966.4	ENSP00000256442.5		P14635-1

Frequencies

GnomAD3 genomes

AF:

0.000394

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000491

AC:

123

AN:

250412

Hom.:

AF XY:

0.000495

AC XY:

AN XY:

135378

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000468

Gnomad ASJ exome

AF:

0.000699

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000822

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000582

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.000392

AC:

573

AN:

1461176

Hom.:

Cov.:

AF XY:

0.000435

AC XY:

316

AN XY:

726886

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.000517

Gnomad4 ASJ exome

AF:

0.000613

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000755

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000365

Gnomad4 OTH exome

AF:

0.000762

GnomAD4 genome

AF:

0.000394

AC:

AN:

152348

Hom.:

Cov.:

AF XY:

0.000403

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000456

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000548

Hom.:

Bravo

AF:

0.000427

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000420

AC:

EpiCase

AF:

0.00142

EpiControl

AF:

0.00107

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 02, 2021

The c.186G>T (p.M62I) alteration is located in exon 2 (coding exon 2) of the CCNB1 gene. This alteration results from a G to T substitution at nucleotide position 186, causing the methionine (M) at amino acid position 62 to be replaced by an isoleucine (I). 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

0.10

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.041

T;T;T;.

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.63

T;T;T;T

M_CAP

Benign

0.0061

MetaRNN

Benign

0.023

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.14

N;.;.;N

PrimateAI

Benign

0.29

PROVEAN

Benign

0.22

N;N;N;N

REVEL

Benign

0.031

Sift

Benign

0.32

T;T;T;T

Sift4G

Benign

0.39

T;T;T;T

Polyphen

0.0

B;B;.;.

Vest4

0.16

MutPred

0.20

Loss of helix (P = 0.0033);Loss of helix (P = 0.0033);Loss of helix (P = 0.0033);Loss of helix (P = 0.0033);

MVP

0.84

MPC

0.055

ClinPred

0.0092

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.072

gMVP

0.10

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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