5-55172296-A-T

Variant names:

• chr5-55172296-A-T
• rs35770269
• NM_001170402.1:c.126+292T>A

Variant summary

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

The NM_001170402.1(CDC20B):​c.126+292T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 325,882 control chromosomes in the GnomAD database, including 13,700 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 0.24 (5275 hom., cov: 32)
  • Exomes 𝑓: 0.30 (8425 hom.)
• Consequence: CDC20B NM_001170402.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850
• Publications: 15 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]

MIR449C (HGNC:37302): (microRNA 449c) 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.342 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+292T>A		intron	N/A	NP_001163873.1	Q86Y33-1
	CDC20B	NM_152623.2		c.126+292T>A		intron	N/A	NP_689836.2	Q86Y33-2
	CDC20B	NM_001145734.2		c.126+292T>A		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+292T>A		intron	N/A	ENSP00000370781.2	Q86Y33-1
	CDC20B	ENST00000296733.5	TSL:1	c.126+292T>A		intron	N/A	ENSP00000296733.1	Q86Y33-2
	CDC20B	ENST00000322374.10	TSL:1	c.126+292T>A		intron	N/A	ENSP00000315720.6	Q86Y33-3

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36065 AN: 151964 Hom.: 5272 Cov.: 32

Gnomad AFR AF: 0.0603

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.355

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.197

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.233

GnomAD2 exomes AF: 0.300 AC: 9047 AN: 30206 AF XY: 0.306

Gnomad AFR exome AF: 0.0584

Gnomad AMR exome AF: 0.363

Gnomad ASJ exome AF: 0.229

Gnomad EAS exome AF: 0.367

Gnomad FIN exome AF: 0.219

Gnomad NFE exome AF: 0.328

Gnomad OTH exome AF: 0.307

GnomAD4 exome AF: 0.300 AC: 52172 AN: 173798 Hom.: 8425 Cov.: 0 AF XY: 0.296 AC XY: 27482 AN XY: 92836

African (AFR) AF: 0.0626 AC: 247 AN: 3944

American (AMR) AF: 0.360 AC: 2299 AN: 6386

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 1267 AN: 5142

East Asian (EAS) AF: 0.384 AC: 3295 AN: 8576

South Asian (SAS) AF: 0.260 AC: 5748 AN: 22080

European-Finnish (FIN) AF: 0.216 AC: 2014 AN: 9308

Middle Eastern (MID) AF: 0.241 AC: 567 AN: 2352

European-Non Finnish (NFE) AF: 0.321 AC: 34006 AN: 106050

Other (OTH) AF: 0.274 AC: 2729 AN: 9960

GnomAD4 genome AF: 0.237 AC: 36078 AN: 152084 Hom.: 5275 Cov.: 32 AF XY: 0.233 AC XY: 17344 AN XY: 74316

African (AFR) AF: 0.0602 AC: 2499 AN: 41526

American (AMR) AF: 0.319 AC: 4872 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 843 AN: 3470

East Asian (EAS) AF: 0.355 AC: 1835 AN: 5166

South Asian (SAS) AF: 0.262 AC: 1263 AN: 4812

European-Finnish (FIN) AF: 0.211 AC: 2233 AN: 10562

Middle Eastern (MID) AF: 0.199 AC: 58 AN: 292

European-Non Finnish (NFE) AF: 0.317 AC: 21538 AN: 67970

Other (OTH) AF: 0.236 AC: 497 AN: 2108

Alfa AF: 0.274 Hom.: 762

Bravo AF: 0.239

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	2.9
DANN	Benign	0.70
PhyloP100		0.085
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: rs35770269; hg19: chr5-54468124; COSMIC: COSV57058374; COSMIC: COSV57058374;