5-138306341-C-T

Variant names:

• chr5-138306341-C-T
• rs6596428
• NM_001790.5:c.615+12878G>A

Variant summary

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

The NM_001790.5(CDC25C):​c.615+12878G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 151,500 control chromosomes in the GnomAD database, including 16,635 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 0.45 (16635 hom., cov: 31)
• Consequence: CDC25C NM_001790.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.846
• Publications: 9 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDC25C	NM_001790.5	c.615+12878G>A		intron_variant	Intron 7 of 13	ENST00000323760.11	NP_001781.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC25C	ENST00000323760.11	c.615+12878G>A		intron_variant	Intron 7 of 13	1	NM_001790.5	ENSP00000321656.6

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68178 AN: 151382 Hom.: 16621 Cov.: 31

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.450 AC: 68223 AN: 151500 Hom.: 16635 Cov.: 31 AF XY: 0.448 AC XY: 33176 AN XY: 73978

African (AFR) AF: 0.267 AC: 11049 AN: 41394

American (AMR) AF: 0.475 AC: 7225 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 1511 AN: 3462

East Asian (EAS) AF: 0.301 AC: 1557 AN: 5168

South Asian (SAS) AF: 0.681 AC: 3277 AN: 4810

European-Finnish (FIN) AF: 0.460 AC: 4800 AN: 10434

Middle Eastern (MID) AF: 0.418 AC: 122 AN: 292

European-Non Finnish (NFE) AF: 0.554 AC: 37502 AN: 67720

Other (OTH) AF: 0.421 AC: 887 AN: 2106

Alfa AF: 0.532 Hom.: 4418

Bravo AF: 0.437

Asia WGS AF: 0.488 AC: 1695 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.44
DANN	Benign	0.59
PhyloP100		-0.85
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6596428; hg19: chr5-137642030;