rs839763

chr1-43359973-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001255.3(CDC20):c.432T>C(p.Tyr144=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 1,613,612 control chromosomes in the GnomAD database, including 106,147 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 0.33 (8486 hom., cov: 32)
  • Exomes 𝑓: 0.36 (97661 hom.)
• Consequence: CDC20 NM_001255.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.297

Genes affected

CDC20 (HGNC:1723): (cell division cycle 20) CDC20 appears to act as a regulatory protein interacting with several other proteins at multiple points in the cell cycle. It is required for two microtubule-dependent processes, nuclear movement prior to anaphase and chromosome separation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP7: Synonymous conserved (PhyloP=0.297 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDC20	NM_001255.3	c.432T>C	p.Tyr144=	synonymous_variant	5/11	ENST00000310955.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDC20	ENST00000310955.11	c.432T>C	p.Tyr144=	synonymous_variant	5/11	1	NM_001255.3	P1
CDC20	ENST00000372462.1	c.432T>C	p.Tyr144=	synonymous_variant	4/10	1		P1
CDC20	ENST00000478882.1	n.207T>C		non_coding_transcript_exon_variant	1/4	2

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49746 AN: 151976 Hom.: 8483 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.0984

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.379

GnomAD3 exomes AF: 0.310 AC: 78054 AN: 251382 Hom.: 13431 AF XY: 0.308 AC XY: 41785 AN XY: 135864

Gnomad AFR exome AF: 0.269

Gnomad AMR exome AF: 0.305

Gnomad ASJ exome AF: 0.416

Gnomad EAS exome AF: 0.0947

Gnomad SAS exome AF: 0.153

Gnomad FIN exome AF: 0.333

Gnomad NFE exome AF: 0.380

Gnomad OTH exome AF: 0.350

GnomAD4 exome AF: 0.358 AC: 522899 AN: 1461518 Hom.: 97661 Cov.: 40 AF XY: 0.352 AC XY: 256284 AN XY: 727052

Gnomad4 AFR exome AF: 0.280

Gnomad4 AMR exome AF: 0.316

Gnomad4 ASJ exome AF: 0.410

Gnomad4 EAS exome AF: 0.116

Gnomad4 SAS exome AF: 0.158

Gnomad4 FIN exome AF: 0.324

Gnomad4 NFE exome AF: 0.387

Gnomad4 OTH exome AF: 0.348

GnomAD4 genome AF: 0.327 AC: 49777 AN: 152094 Hom.: 8486 Cov.: 32 AF XY: 0.323 AC XY: 23988 AN XY: 74360

Gnomad4 AFR AF: 0.272

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.406

Gnomad4 EAS AF: 0.0982

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.332

Gnomad4 NFE AF: 0.373

Gnomad4 OTH AF: 0.377

Alfa AF: 0.362 Hom.: 7303

Bravo AF: 0.330

Asia WGS AF: 0.146 AC: 510 AN: 3478

EpiCase AF: 0.385

EpiControl AF: 0.386

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	12
Dann	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs839763; hg19: chr1-43825644; COSMIC: COSV60521684; COSMIC: COSV60521684;