rs164390

Variant names:

• chr5-69167187-G-T
• rs164390
• NM_031966.4:c.-76G>T

Variant summary

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

The NM_031966.4(CCNB1):​c.-76G>T variant causes a 5 prime UTR premature start codon gain 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_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.946
• Publications: 23 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]

ENSG00000248664 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCNB1	NM_031966.4	MANE Select	c.-76G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	NP_114172.1
	CCNB1	NM_031966.4	MANE Select	c.-76G>T		5_prime_UTR	Exon 1 of 9	NP_114172.1
	CCNB1	NM_001354844.2		c.-76G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	NP_001341773.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCNB1	ENST00000256442.10	TSL:1 MANE Select	c.-76G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	ENSP00000256442.5
	CCNB1	ENST00000506572.5	TSL:1	c.-76G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	ENSP00000423387.1
	CCNB1	ENST00000256442.10	TSL:1 MANE Select	c.-76G>T		5_prime_UTR	Exon 1 of 9	ENSP00000256442.5

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

African (AFR) AF: 0.459 AC: 11615 AN: 25306

American (AMR) AF: 0.445 AC: 12227 AN: 27474

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 6971 AN: 18636

East Asian (EAS) AF: 0.514 AC: 17446 AN: 33912

South Asian (SAS) AF: 0.542 AC: 35559 AN: 65588

European-Finnish (FIN) AF: 0.394 AC: 17899 AN: 45422

Middle Eastern (MID) AF: 0.409 AC: 1352 AN: 3306

European-Non Finnish (NFE) AF: 0.406 AC: 361344 AN: 890666

Other (OTH) AF: 0.417 AC: 20411 AN: 48912

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

African (AFR) AF: 0.452 AC: 18777 AN: 41500

American (AMR) AF: 0.449 AC: 6867 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1272 AN: 3466

East Asian (EAS) AF: 0.458 AC: 2367 AN: 5164

South Asian (SAS) AF: 0.550 AC: 2652 AN: 4822

European-Finnish (FIN) AF: 0.381 AC: 4030 AN: 10580

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.407 AC: 27652 AN: 67986

Other (OTH) AF: 0.413 AC: 869 AN: 2106

Alfa AF: 0.411 Hom.: 15897

Bravo AF: 0.431

Asia WGS AF: 0.519 AC: 1803 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.4
DANN	Benign	0.60
PhyloP100		-0.95
PromoterAI		-0.020	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs164390; hg19: chr5-68463014; COSMIC: COSV104374153; COSMIC: COSV104374153;