20-3795528-C-T

Variant names:

• chr20-3795528-C-T
• rs3761218
• NM_001287516.2:c.9-2094C>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.9-2094C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.65 in 152,162 control chromosomes in the GnomAD database, including 32,331 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 0.65 (32331 hom., cov: 33)
• Consequence: CDC25B NM_001287516.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0740
• Publications: 37 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDC25B	NM_001287516.2	c.9-2094C>T		intron_variant	Intron 1 of 15		NP_001274445.1
CDC25B	NM_001287517.2	c.9-2136C>T		intron_variant	Intron 1 of 15		NP_001274446.1
CDC25B	NM_001287518.2	c.9-2094C>T		intron_variant	Intron 1 of 14		NP_001274447.1
CDC25B	NR_136336.2	n.190-2094C>T		intron_variant	Intron 1 of 16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC25B	ENST00000344256.10	c.9-2094C>T		intron_variant	Intron 1 of 15	2		ENSP00000339125.6
CDC25B	ENST00000379598.9	c.9-2094C>T		intron_variant	Intron 1 of 14	2		ENSP00000368918.5
CDC25B	ENST00000467519.5	n.-211C>T		upstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.650 AC: 98788 AN: 152044 Hom.: 32312 Cov.: 33

Gnomad AFR AF: 0.732

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.609

Gnomad OTH AF: 0.600

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

GnomAD4 genome AF: 0.650 AC: 98865 AN: 152162 Hom.: 32331 Cov.: 33 AF XY: 0.650 AC XY: 48379 AN XY: 74406

African (AFR) AF: 0.732 AC: 30370 AN: 41512

American (AMR) AF: 0.627 AC: 9591 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 2239 AN: 3472

East Asian (EAS) AF: 0.692 AC: 3583 AN: 5180

South Asian (SAS) AF: 0.570 AC: 2751 AN: 4826

European-Finnish (FIN) AF: 0.665 AC: 7032 AN: 10582

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.609 AC: 41375 AN: 67974

Other (OTH) AF: 0.595 AC: 1257 AN: 2114

Alfa AF: 0.619 Hom.: 123089

Bravo AF: 0.653

Asia WGS AF: 0.633 AC: 2201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.9
DANN	Benign	0.65
PhyloP100		-0.074
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: rs3761218; hg19: chr20-3776175;