rs336081

Positions:

• chr5-55137565-G-A
• chr5-55137565-G-C

Variant summary

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

The NM_001170402.1(CDC20B):​c.580+2749C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 456,418 control chromosomes in the GnomAD database, including 86,313 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 0.60 (27563 hom., cov: 32)
  • Exomes 𝑓: 0.62 (58750 hom.)
• Consequence: CDC20B NM_001170402.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.222

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC20B	NM_001170402.1	c.580+2749C>T		intron_variant		ENST00000381375.7	NP_001163873.1
CDC20B	NM_152623.2	c.580+2749C>T		intron_variant			NP_689836.2
CDC20B	NM_001145734.2	c.580+2749C>T		intron_variant			NP_001139206.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC20B	ENST00000381375.7	c.580+2749C>T		intron_variant		1	NM_001170402.1	ENSP00000370781.2

Frequencies

GnomAD3 genomes AF: 0.599 AC: 90913 AN: 151896 Hom.: 27544 Cov.: 32

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.660

Gnomad AMR AF: 0.690

Gnomad ASJ AF: 0.656

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.555

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.637

Gnomad OTH AF: 0.607

GnomAD3 exomes AF: 0.623 AC: 85391 AN: 137002 Hom.: 26985 AF XY: 0.617 AC XY: 45983 AN XY: 74484

Gnomad AFR exome AF: 0.505

Gnomad AMR exome AF: 0.740

Gnomad ASJ exome AF: 0.657

Gnomad EAS exome AF: 0.528

Gnomad SAS exome AF: 0.548

Gnomad FIN exome AF: 0.559

Gnomad NFE exome AF: 0.636

Gnomad OTH exome AF: 0.636

GnomAD4 exome AF: 0.618 AC: 188105 AN: 304402 Hom.: 58750 Cov.: 0 AF XY: 0.612 AC XY: 106018 AN XY: 173332

Gnomad4 AFR exome AF: 0.513

Gnomad4 AMR exome AF: 0.741

Gnomad4 ASJ exome AF: 0.658

Gnomad4 EAS exome AF: 0.537

Gnomad4 SAS exome AF: 0.551

Gnomad4 FIN exome AF: 0.553

Gnomad4 NFE exome AF: 0.635

Gnomad4 OTH exome AF: 0.614

GnomAD4 genome AF: 0.598 AC: 90978 AN: 152016 Hom.: 27563 Cov.: 32 AF XY: 0.595 AC XY: 44198 AN XY: 74288

Gnomad4 AFR AF: 0.517

Gnomad4 AMR AF: 0.690

Gnomad4 ASJ AF: 0.656

Gnomad4 EAS AF: 0.549

Gnomad4 SAS AF: 0.547

Gnomad4 FIN AF: 0.555

Gnomad4 NFE AF: 0.637

Gnomad4 OTH AF: 0.610

Alfa AF: 0.599 Hom.: 7032

Bravo AF: 0.605

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.067
DANN	Benign	0.31

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: rs336081; hg19: chr5-54433393; COSMIC: COSV104393354;