5-69167279-C-T

Variant names:

• chr5-69167279-C-T
• rs369118449
• NM_031966.4:c.17C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_031966.4(CCNB1):​c.17C>T​(p.Thr6Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000698 in 1,431,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. T6S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: CCNB1 NM_031966.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.89
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37509066).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCNB1	NM_031966.4	MANE Select	c.17C>T	p.Thr6Ile	missense	Exon 1 of 9	NP_114172.1	P14635-1
	CCNB1	NM_001354844.2		c.17C>T	p.Thr6Ile	missense	Exon 1 of 8	NP_001341773.1	P14635-2
	CCNB1	NM_001354845.2		c.17C>T	p.Thr6Ile	missense	Exon 1 of 8	NP_001341774.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCNB1	ENST00000256442.10	TSL:1 MANE Select	c.17C>T	p.Thr6Ile	missense	Exon 1 of 9	ENSP00000256442.5	P14635-1
	CCNB1	ENST00000506572.5	TSL:1	c.17C>T	p.Thr6Ile	missense	Exon 1 of 8	ENSP00000423387.1	E9PC90
	CCNB1	ENST00000505500.5	TSL:1	c.17C>T	p.Thr6Ile	missense	Exon 1 of 8	ENSP00000424588.1	P14635-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1431770 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 711514

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32354

American (AMR) AF: 0.00 AC: 0 AN: 40812

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24976

East Asian (EAS) AF: 0.00 AC: 0 AN: 38120

South Asian (SAS) AF: 0.00 AC: 0 AN: 83140

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49170

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4168

European-Non Finnish (NFE) AF: 9.09e-7 AC: 1 AN: 1099894

Other (OTH) AF: 0.00 AC: 0 AN: 59136

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.45	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		1.9
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.25
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.010	D
Polyphen		0.99	D
Vest4		0.45
MutPred		0.43		Gain of relative solvent accessibility (P = 0.0522)
MVP		0.89
MPC		0.10
ClinPred		0.98	D
GERP RS		3.8
PromoterAI		0.13	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.29
gMVP		0.73
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs369118449; hg19: chr5-68463106;