chr5-69168227-C-T

Position:

• chr5-69168227-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031966.4(CCNB1):​c.247C>T​(p.Leu83Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CCNB1 NM_031966.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0740

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

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=0.14481643).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCNB1	NM_031966.4	c.247C>T	p.Leu83Phe	missense_variant	3/9	ENST00000256442.10	NP_114172.1
CCNB1	NM_001354844.2	c.247C>T	p.Leu83Phe	missense_variant	3/8		NP_001341773.1
CCNB1	NM_001354845.2	c.247C>T	p.Leu83Phe	missense_variant	3/8		NP_001341774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCNB1	ENST00000256442.10	c.247C>T	p.Leu83Phe	missense_variant	3/9	1	NM_031966.4	ENSP00000256442.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 19, 2024

The c.247C>T (p.L83F) alteration is located in exon 3 (coding exon 3) of the CCNB1 gene. This alteration results from a C to T substitution at nucleotide position 247, causing the leucine (L) at amino acid position 83 to be replaced by a phenylalanine (F). 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	0.087
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;T;T;.
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.74	T;T;T;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.14	T;T;T;T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	1.8	L;.;.;L
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.6	N;N;N;N
REVEL	Benign	0.21
Sift	Benign	0.063	T;T;D;T
Sift4G	Benign	0.14	T;T;T;T
Polyphen		0.23	B;B;.;.
Vest4		0.18
MutPred		0.18		Gain of methylation at K78 (P = 0.1012);Gain of methylation at K78 (P = 0.1012);Gain of methylation at K78 (P = 0.1012);Gain of methylation at K78 (P = 0.1012);
MVP		0.90
MPC		0.087
ClinPred		0.25	T
GERP RS		-2.2
Varity_R		0.065
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-68464054;