rs11567998

chr5-138289452-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001790.5(CDC25C):c.927+49G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0139 in 1,335,852 control chromosomes in the GnomAD database, including 206 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 0.011 (13 hom., cov: 32)
  • Exomes 𝑓: 0.014 (193 hom.)
• Consequence: CDC25C NM_001790.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0660

Genes affected

CDC25C (HGNC:1727): (cell division cycle 25C) This gene encodes a conserved protein that plays a key role in the regulation of cell division. The encoded protein directs dephosphorylation of cyclin B-bound CDC2 and triggers entry into mitosis. It also suppresses p53-induced growth arrest. Multiple alternatively spliced transcript variants of this gene have been described. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0105 (1599/152212) while in subpopulation NFE AF= 0.0163 (1107/68026). AF 95% confidence interval is 0.0155. There are 13 homozygotes in gnomad4. There are 705 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 13 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDC25C	NM_001790.5	c.927+49G>C		intron_variant		ENST00000323760.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDC25C	ENST00000323760.11	c.927+49G>C		intron_variant		1	NM_001790.5	P2

Frequencies

GnomAD3 genomes AF: 0.0105 AC: 1600 AN: 152094 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.00307

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0153

Gnomad ASJ AF: 0.0156

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00435

Gnomad FIN AF: 0.00189

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0163

Gnomad OTH AF: 0.0163

GnomAD3 exomes AF: 0.0101 AC: 2539 AN: 250698 Hom.: 24 AF XY: 0.0105 AC XY: 1425 AN XY: 135498

Gnomad AFR exome AF: 0.00277

Gnomad AMR exome AF: 0.0100

Gnomad ASJ exome AF: 0.0128

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00530

Gnomad FIN exome AF: 0.00213

Gnomad NFE exome AF: 0.0153

Gnomad OTH exome AF: 0.0125

GnomAD4 exome AF: 0.0143 AC: 16908 AN: 1183640 Hom.: 193 Cov.: 17 AF XY: 0.0140 AC XY: 8431 AN XY: 602026

Gnomad4 AFR exome AF: 0.00327

Gnomad4 AMR exome AF: 0.0104

Gnomad4 ASJ exome AF: 0.0136

Gnomad4 EAS exome AF: 0.0000260

Gnomad4 SAS exome AF: 0.00502

Gnomad4 FIN exome AF: 0.00237

Gnomad4 NFE exome AF: 0.0171

Gnomad4 OTH exome AF: 0.0153

GnomAD4 genome AF: 0.0105 AC: 1599 AN: 152212 Hom.: 13 Cov.: 32 AF XY: 0.00947 AC XY: 705 AN XY: 74422

Gnomad4 AFR AF: 0.00306

Gnomad4 AMR AF: 0.0153

Gnomad4 ASJ AF: 0.0156

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00414

Gnomad4 FIN AF: 0.00189

Gnomad4 NFE AF: 0.0163

Gnomad4 OTH AF: 0.0161

Alfa AF: 0.0123 Hom.: 2

Bravo AF: 0.0113

Asia WGS AF: 0.00144 AC: 6 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
Cadd	Benign	17
Dann	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs11567998; hg19: chr5-137625141;