chr5-69171680-T-C

Variant names:

• chr5-69171680-T-C
• rs2069433
• NM_031966.4:c.546+228T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031966.4(CCNB1):​c.546+228T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,174 control chromosomes in the GnomAD database, including 1,093 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (1093 hom., cov: 33)
• Consequence: CCNB1 NM_031966.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124
• Publications: 8 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCNB1	NM_031966.4	c.546+228T>C		intron_variant	Intron 4 of 8	ENST00000256442.10	NP_114172.1
CCNB1	NM_001354844.2	c.546+228T>C		intron_variant	Intron 4 of 7		NP_001341773.1
CCNB1	NM_001354845.2	c.546+228T>C		intron_variant	Intron 4 of 7		NP_001341774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCNB1	ENST00000256442.10	c.546+228T>C		intron_variant	Intron 4 of 8	1	NM_031966.4	ENSP00000256442.5

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16409 AN: 152056 Hom.: 1091 Cov.: 33

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.0829

Gnomad EAS AF: 0.0721

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.0350

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0747

Gnomad OTH AF: 0.0961

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.108 AC: 16419 AN: 152174 Hom.: 1093 Cov.: 33 AF XY: 0.108 AC XY: 8069 AN XY: 74394

African (AFR) AF: 0.170 AC: 7048 AN: 41510

American (AMR) AF: 0.134 AC: 2051 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0829 AC: 288 AN: 3472

East Asian (EAS) AF: 0.0719 AC: 372 AN: 5174

South Asian (SAS) AF: 0.181 AC: 875 AN: 4826

European-Finnish (FIN) AF: 0.0350 AC: 371 AN: 10592

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0747 AC: 5084 AN: 68020

Other (OTH) AF: 0.0951 AC: 201 AN: 2114

Alfa AF: 0.0897 Hom.: 956

Bravo AF: 0.116

Asia WGS AF: 0.162 AC: 563 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.0
DANN	Benign	0.29
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

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: rs2069433; hg19: chr5-68467507; COSMIC: COSV104374140;