chr5-69167996-C-T

Position:

• chr5-69167996-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.110C>T​(p.Pro37Leu) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CCNB1 NM_031966.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.15

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=0.2506864).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCNB1	NM_031966.4	c.110C>T	p.Pro37Leu	missense_variant	2/9	ENST00000256442.10	NP_114172.1
CCNB1	NM_001354844.2	c.110C>T	p.Pro37Leu	missense_variant	2/8		NP_001341773.1
CCNB1	NM_001354845.2	c.110C>T	p.Pro37Leu	missense_variant	2/8		NP_001341774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCNB1	ENST00000256442.10	c.110C>T	p.Pro37Leu	missense_variant	2/9	1	NM_031966.4	ENSP00000256442.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

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

Dec 15, 2023

The c.110C>T (p.P37L) alteration is located in exon 2 (coding exon 2) of the CCNB1 gene. This alteration results from a C to T substitution at nucleotide position 110, causing the proline (P) at amino acid position 37 to be replaced by a leucine (L). 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	0.13
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T;T;T;.
Eigen	Benign	0.086
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.87	D;D;D;D
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.25	T;T;T;T
MetaSVM	Benign	-0.72	T
MutationAssessor	Uncertain	2.9	M;.;.;M
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.2	D;D;D;D
REVEL	Benign	0.12
Sift	Uncertain	0.0070	D;D;D;D
Sift4G	Uncertain	0.0070	D;D;D;D
Polyphen		0.077	B;P;.;.
Vest4		0.34
MutPred		0.26		Gain of MoRF binding (P = 0.0453);Gain of MoRF binding (P = 0.0453);Gain of MoRF binding (P = 0.0453);Gain of MoRF binding (P = 0.0453);
MVP		0.80
MPC		0.055
ClinPred		0.97	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.096
gMVP		0.71

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

Other links and lift over

dbSNP: rs1747375175; hg19: chr5-68463823;