chr20-3791880-A-T

Position:

• chr20-3791880-A-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC25B	NM_001287516.2	c.8+4741A>T		intron_variant			NP_001274445.1
CDC25B	NM_001287517.2	c.8+4741A>T		intron_variant			NP_001274446.1
CDC25B	NM_001287518.2	c.8+4741A>T		intron_variant			NP_001274447.1
CDC25B	NR_136336.2	n.189+4741A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC25B	ENST00000344256.10	c.8+4741A>T		intron_variant		2		ENSP00000339125
CDC25B	ENST00000379598.9	c.8+4741A>T		intron_variant		2		ENSP00000368918

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

Gnomad4 AFR AF: 0.884

Gnomad4 AMR AF: 0.644

Gnomad4 ASJ AF: 0.646

Gnomad4 EAS AF: 0.692

Gnomad4 SAS AF: 0.572

Gnomad4 FIN AF: 0.664

Gnomad4 NFE AF: 0.609

Gnomad4 OTH AF: 0.637

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	6.2
DANN	Benign	0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4815603; hg19: chr20-3772527;