5-69171433-C-T

Variant names:

• chr5-69171433-C-T
• NM_031966.4:c.527C>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.527C>T​(p.Ala176Val) 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. 15/22 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: 0.00300
• 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=0.15279084).

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.527C>T	p.Ala176Val	missense	Exon 4 of 9	NP_114172.1	P14635-1
	CCNB1	NM_001354844.2		c.527C>T	p.Ala176Val	missense	Exon 4 of 8	NP_001341773.1	P14635-2
	CCNB1	NM_001354845.2		c.527C>T	p.Ala176Val	missense	Exon 4 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.527C>T	p.Ala176Val	missense	Exon 4 of 9	ENSP00000256442.5	P14635-1
	CCNB1	ENST00000506572.5	TSL:1	c.527C>T	p.Ala176Val	missense	Exon 4 of 8	ENSP00000423387.1	E9PC90
	CCNB1	ENST00000505500.5	TSL:1	c.527C>T	p.Ala176Val	missense	Exon 4 of 8	ENSP00000424588.1	P14635-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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	0.093
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.0030
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.054
Sift	Benign	0.29	T
Sift4G	Benign	0.28	T
Polyphen		0.018	B
Vest4		0.12
MutPred		0.50		Gain of methylation at K172 (P = 0.1204)
MVP		0.82
MPC		0.053
ClinPred		0.21	T
GERP RS		3.0
Varity_R		0.15
gMVP		0.26
Mutation Taster		=80/20	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

hg19: chr5-68467260;