chr5-69167996-C-T

Variant names:

• chr5-69167996-C-T
• rs1747375175
• NM_031966.4:c.110C>T

Variant summary

Our verdict is Uncertain significance. The variant received 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. 13/22 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
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2506864).

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.110C>T	p.Pro37Leu	missense	Exon 2 of 9	NP_114172.1	P14635-1
	CCNB1	NM_001354844.2		c.110C>T	p.Pro37Leu	missense	Exon 2 of 8	NP_001341773.1	P14635-2
	CCNB1	NM_001354845.2		c.110C>T	p.Pro37Leu	missense	Exon 2 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.110C>T	p.Pro37Leu	missense	Exon 2 of 9	ENSP00000256442.5	P14635-1
	CCNB1	ENST00000506572.5	TSL:1	c.110C>T	p.Pro37Leu	missense	Exon 2 of 8	ENSP00000423387.1	E9PC90
	CCNB1	ENST00000505500.5	TSL:1	c.110C>T	p.Pro37Leu	missense	Exon 2 of 8	ENSP00000424588.1	P14635-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	0.086
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.72	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		3.1
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.12
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.077	B
Vest4		0.34
MutPred		0.26		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
Mutation Taster		=77/23	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: rs1747375175; hg19: chr5-68463823;