rs10061133

Variant names:

• chr5-55170716-A-G
• rs10061133
• NM_001170402.1:c.126+1872T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001170402.1(CDC20B):​c.126+1872T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 534,034 control chromosomes in the GnomAD database, including 3,328 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 0.089 (743 hom., cov: 33)
  • Exomes 𝑓: 0.11 (2585 hom.)
• Consequence: CDC20B NM_001170402.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.54
• Publications: 49 publications found

Genes affected

CDC20B (HGNC:24222): (cell division cycle 20B) Predicted to enable anaphase-promoting complex binding activity and ubiquitin ligase activator activity. Predicted to be involved in anaphase-promoting complex-dependent catabolic process and positive regulation of anaphase-promoting complex-dependent catabolic process. Predicted to be part of anaphase-promoting complex. [provided by Alliance of Genome Resources, Apr 2022]

MIR449B (HGNC:32794): (microRNA 449b) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR449A (HGNC:27645): (microRNA 449a) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001170402.1. 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
	CDC20B	NM_001170402.1	MANE Select	c.126+1872T>C		intron	N/A	NP_001163873.1	Q86Y33-1
	CDC20B	NM_152623.2		c.126+1872T>C		intron	N/A	NP_689836.2	Q86Y33-2
	CDC20B	NM_001145734.2		c.126+1872T>C		intron	N/A	NP_001139206.2	Q86Y33-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC20B	ENST00000381375.7	TSL:1 MANE Select	c.126+1872T>C		intron	N/A	ENSP00000370781.2	Q86Y33-1
	CDC20B	ENST00000296733.5	TSL:1	c.126+1872T>C		intron	N/A	ENSP00000296733.1	Q86Y33-2
	CDC20B	ENST00000322374.10	TSL:1	c.126+1872T>C		intron	N/A	ENSP00000315720.6	Q86Y33-3

Frequencies

GnomAD3 genomes AF: 0.0890 AC: 13534 AN: 152126 Hom.: 743 Cov.: 33

Gnomad AFR AF: 0.0447

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.0707

Gnomad ASJ AF: 0.0825

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.0918

GnomAD2 exomes AF: 0.107 AC: 26784 AN: 250436 AF XY: 0.111

Gnomad AFR exome AF: 0.0450

Gnomad AMR exome AF: 0.0479

Gnomad ASJ exome AF: 0.0806

Gnomad EAS exome AF: 0.264

Gnomad FIN exome AF: 0.115

Gnomad NFE exome AF: 0.103

Gnomad OTH exome AF: 0.110

GnomAD4 exome AF: 0.106 AC: 40312 AN: 381790 Hom.: 2585 Cov.: 0 AF XY: 0.109 AC XY: 23694 AN XY: 217244

African (AFR) AF: 0.0448 AC: 471 AN: 10510

American (AMR) AF: 0.0476 AC: 1726 AN: 36292

Ashkenazi Jewish (ASJ) AF: 0.0805 AC: 945 AN: 11740

East Asian (EAS) AF: 0.260 AC: 3425 AN: 13152

South Asian (SAS) AF: 0.126 AC: 8378 AN: 66754

European-Finnish (FIN) AF: 0.113 AC: 3650 AN: 32282

Middle Eastern (MID) AF: 0.141 AC: 401 AN: 2842

European-Non Finnish (NFE) AF: 0.102 AC: 19587 AN: 191528

Other (OTH) AF: 0.104 AC: 1729 AN: 16690

GnomAD4 genome AF: 0.0889 AC: 13537 AN: 152244 Hom.: 743 Cov.: 33 AF XY: 0.0903 AC XY: 6718 AN XY: 74436

African (AFR) AF: 0.0448 AC: 1863 AN: 41566

American (AMR) AF: 0.0706 AC: 1080 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0825 AC: 286 AN: 3468

East Asian (EAS) AF: 0.258 AC: 1337 AN: 5176

South Asian (SAS) AF: 0.132 AC: 635 AN: 4822

European-Finnish (FIN) AF: 0.109 AC: 1156 AN: 10590

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6854 AN: 68012

Other (OTH) AF: 0.0932 AC: 197 AN: 2114

Alfa AF: 0.0867 Hom.: 438

Bravo AF: 0.0833

Asia WGS AF: 0.186 AC: 650 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	15
DANN	Benign	0.86
PhyloP100		2.5
Mutation Taster		=97/3	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: rs10061133; hg19: chr5-54466544; COSMIC: COSV57051787; COSMIC: COSV57051787;