rs164390

Positions:

• chr5-69167187-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031966.4(CCNB1):​c.-76G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 1,311,346 control chromosomes in the GnomAD database, including 116,800 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 0.43 (14034 hom., cov: 33)
  • Exomes 𝑓: 0.42 (102766 hom.)
• Consequence: CCNB1 NM_031966.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.946

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCNB1	NM_031966.4	c.-76G>T		5_prime_UTR_variant	1/9	ENST00000256442.10
CCNB1	NM_001354844.2	c.-76G>T		5_prime_UTR_variant	1/8
CCNB1	NM_001354845.2	c.-76G>T		5_prime_UTR_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCNB1	ENST00000256442.10	c.-76G>T		5_prime_UTR_variant	1/9	1	NM_031966.4	P1
CCNB1	ENST00000506572.5	c.-76G>T		5_prime_UTR_variant	1/8	1
CCNB1	ENST00000508407.5			upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65161 AN: 152006 Hom.: 14020 Cov.: 33

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.411

GnomAD4 exome AF: 0.418 AC: 484824 AN: 1159222 Hom.: 102766 Cov.: 15 AF XY: 0.421 AC XY: 242807 AN XY: 576556

Gnomad4 AFR exome AF: 0.459

Gnomad4 AMR exome AF: 0.445

Gnomad4 ASJ exome AF: 0.374

Gnomad4 EAS exome AF: 0.514

Gnomad4 SAS exome AF: 0.542

Gnomad4 FIN exome AF: 0.394

Gnomad4 NFE exome AF: 0.406

Gnomad4 OTH exome AF: 0.417

GnomAD4 genome AF: 0.429 AC: 65202 AN: 152124 Hom.: 14034 Cov.: 33 AF XY: 0.430 AC XY: 32007 AN XY: 74356

Gnomad4 AFR AF: 0.452

Gnomad4 AMR AF: 0.449

Gnomad4 ASJ AF: 0.367

Gnomad4 EAS AF: 0.458

Gnomad4 SAS AF: 0.550

Gnomad4 FIN AF: 0.381

Gnomad4 NFE AF: 0.407

Gnomad4 OTH AF: 0.413

Alfa AF: 0.407 Hom.: 11776

Bravo AF: 0.431

Asia WGS AF: 0.519 AC: 1803 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.4
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs164390; hg19: chr5-68463014; COSMIC: COSV104374153; COSMIC: COSV104374153;