rs17171794

Positions:

• chr5-138310489-C-A
• chr5-138310489-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001790.5(CDC25C):​c.615+8730G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 152,046 control chromosomes in the GnomAD database, including 7,160 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 0.30 (7160 hom., cov: 32)
• Consequence: CDC25C NM_001790.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.338

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC25C	NM_001790.5	c.615+8730G>T		intron_variant		ENST00000323760.11	NP_001781.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC25C	ENST00000323760.11	c.615+8730G>T		intron_variant		1	NM_001790.5	ENSP00000321656.6

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45331 AN: 151928 Hom.: 7155 Cov.: 32

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.605

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.298 AC: 45338 AN: 152046 Hom.: 7160 Cov.: 32 AF XY: 0.305 AC XY: 22677 AN XY: 74314

Gnomad4 AFR AF: 0.294

Gnomad4 AMR AF: 0.324

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.606

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.265

Gnomad4 OTH AF: 0.333

Alfa AF: 0.282 Hom.: 1683

Bravo AF: 0.305

Asia WGS AF: 0.382 AC: 1328 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.1
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs17171794; hg19: chr5-137646178; COSMIC: COSV60398752;