chr5-69167926-G-C

Position:

• chr5-69167926-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_031966.4(CCNB1):​c.40G>C​(p.Glu14Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 6.01

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37644628).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCNB1	NM_031966.4	c.40G>C	p.Glu14Gln	missense_variant	2/9	ENST00000256442.10	NP_114172.1
CCNB1	NM_001354844.2	c.40G>C	p.Glu14Gln	missense_variant	2/8		NP_001341773.1
CCNB1	NM_001354845.2	c.40G>C	p.Glu14Gln	missense_variant	2/8		NP_001341774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCNB1	ENST00000256442.10	c.40G>C	p.Glu14Gln	missense_variant	2/9	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

Jun 29, 2023

The c.40G>C (p.E14Q) alteration is located in exon 2 (coding exon 2) of the CCNB1 gene. This alteration results from a G to C substitution at nucleotide position 40, causing the glutamic acid (E) at amino acid position 14 to be replaced by a glutamine (Q). 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	0.15
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;T;T;.
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.85	D;D;D;D
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.38	T;T;T;T
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.8	M;.;.;M
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.4	N;N;N;N
REVEL	Benign	0.20
Sift	Uncertain	0.014	D;D;D;D
Sift4G	Benign	0.14	T;T;T;T
Polyphen		1.0	D;D;.;.
Vest4		0.35
MutPred		0.28		Loss of stability (P = 0.1592);Loss of stability (P = 0.1592);Loss of stability (P = 0.1592);Loss of stability (P = 0.1592);
MVP		0.92
MPC		0.21
ClinPred		0.97	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.23
gMVP		0.38

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-68463753;