20-3791880-A-T

Variant names:

• chr20-3791880-A-T
• rs4815603
• NM_001287516.2:c.8+4741A>T

Variant summary

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

The NM_001287516.2(CDC25B):​c.8+4741A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.694 in 152,166 control chromosomes in the GnomAD database, including 37,775 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 0.69 (37775 hom., cov: 32)
• Consequence: CDC25B NM_001287516.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0630
• Publications: 10 publications found

Genes affected

CDC25B (HGNC:1726): (cell division cycle 25B) CDC25B is a member of the CDC25 family of phosphatases. CDC25B activates the cyclin dependent kinase CDC2 by removing two phosphate groups and it is required for entry into mitosis. CDC25B shuttles between the nucleus and the cytoplasm due to nuclear localization and nuclear export signals. The protein is nuclear in the M and G1 phases of the cell cycle and moves to the cytoplasm during S and G2. CDC25B has oncogenic properties, although its role in tumor formation has not been determined. Multiple transcript variants for this gene exist. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.877 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001287516.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC25B	NM_001287516.2		c.8+4741A>T		intron	N/A	NP_001274445.1
	CDC25B	NM_001287517.2		c.8+4741A>T		intron	N/A	NP_001274446.1
	CDC25B	NM_001287518.2		c.8+4741A>T		intron	N/A	NP_001274447.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC25B	ENST00000344256.10	TSL:2	c.8+4741A>T		intron	N/A	ENSP00000339125.6
	CDC25B	ENST00000379598.9	TSL:2	c.8+4741A>T		intron	N/A	ENSP00000368918.5

Frequencies

GnomAD3 genomes AF: 0.694 AC: 105516 AN: 152048 Hom.: 37740 Cov.: 32

Gnomad AFR AF: 0.884

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.664

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.609

Gnomad OTH AF: 0.643

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.694 AC: 105614 AN: 152166 Hom.: 37775 Cov.: 32 AF XY: 0.693 AC XY: 51576 AN XY: 74388

African (AFR) AF: 0.884 AC: 36735 AN: 41532

American (AMR) AF: 0.644 AC: 9833 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 2243 AN: 3472

East Asian (EAS) AF: 0.692 AC: 3591 AN: 5190

South Asian (SAS) AF: 0.572 AC: 2762 AN: 4826

European-Finnish (FIN) AF: 0.664 AC: 7023 AN: 10576

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.609 AC: 41413 AN: 67986

Other (OTH) AF: 0.637 AC: 1341 AN: 2106

Alfa AF: 0.510 Hom.: 1298

Bravo AF: 0.703

Asia WGS AF: 0.643 AC: 2235 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	6.2
DANN	Benign	0.76
PhyloP100		0.063
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4815603; hg19: chr20-3772527;