rs10061133

chr5-55170716-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDC20B	NM_001170402.1	c.126+1872T>C		intron_variant		ENST00000381375.7
MIR449B	NR_030387.1	n.27T>C		non_coding_transcript_exon_variant	1/1
CDC20B	NM_001145734.2	c.126+1872T>C		intron_variant
CDC20B	NM_152623.2	c.126+1872T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDC20B	ENST00000381375.7	c.126+1872T>C		intron_variant		1	NM_001170402.1	A1
MIR449B	ENST00000384995.1	n.27T>C		mature_miRNA_variant	1/1

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

GnomAD3 exomes AF: 0.107 AC: 26784 AN: 250436 Hom.: 1826 AF XY: 0.111 AC XY: 15055 AN XY: 135608

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 SAS exome AF: 0.130

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

Gnomad4 AFR exome AF: 0.0448

Gnomad4 AMR exome AF: 0.0476

Gnomad4 ASJ exome AF: 0.0805

Gnomad4 EAS exome AF: 0.260

Gnomad4 SAS exome AF: 0.126

Gnomad4 FIN exome AF: 0.113

Gnomad4 NFE exome AF: 0.102

Gnomad4 OTH exome AF: 0.104

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

Gnomad4 AFR AF: 0.0448

Gnomad4 AMR AF: 0.0706

Gnomad4 ASJ AF: 0.0825

Gnomad4 EAS AF: 0.258

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.0932

Alfa AF: 0.0897 Hom.: 341

Bravo AF: 0.0833

Asia WGS AF: 0.186 AC: 650 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
Cadd	Benign	15
Dann	Benign	0.86

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

Publications

LitVar

Other links and lift over

dbSNP: rs10061133; hg19: chr5-54466544; COSMIC: COSV57051787; COSMIC: COSV57051787;