dbSNP rs11567998: CDC25C:c.927+49G>C (chr5-138289452-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0660

Publications

2 publications found

Variant links:

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]

CDC25C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 13 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDC25C	NM_001790.5 link	c.927+49G>C		intron_variant	Intron 10 of 13	ENST00000323760.11	NP_001781.2	P30307-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC25C	ENST00000323760.11 link	c.927+49G>C		intron_variant	Intron 10 of 13	1	NM_001790.5	ENSP00000321656.6		P30307-1

Frequencies

GnomAD3 genomes

AF:

0.0105

AC:

1600

AN:

152094

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.0101

AC:

2539

AN:

250698

AF XY:

0.0105

show subpopulations

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 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.:

AF XY:

0.0140

AC XY:

8431

AN XY:

602026

show subpopulations

African (AFR)

AF:

0.00327

AC:

AN:

28128

American (AMR)

AF:

0.0104

AC:

462

AN:

44344

Ashkenazi Jewish (ASJ)

AF:

0.0136

AC:

333

AN:

24440

East Asian (EAS)

AF:

0.0000260

AC:

AN:

38426

South Asian (SAS)

AF:

0.00502

AC:

405

AN:

80700

European-Finnish (FIN)

AF:

0.00237

AC:

126

AN:

53272

Middle Eastern (MID)

AF:

0.0110

AC:

AN:

5274

European-Non Finnish (NFE)

AF:

0.0171

AC:

14649

AN:

857794

Other (OTH)

AF:

0.0153

AC:

782

AN:

51262

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

820

1640

2459

3279

4099

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

494

988

1482

1976

2470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0105

AC:

1599

AN:

152212

Hom.:

Cov.:

AF XY:

0.00947

AC XY:

705

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.00306

AC:

127

AN:

41522

American (AMR)

AF:

0.0153

AC:

234

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0156

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.00414

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00189

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0163

AC:

1107

AN:

68026

Other (OTH)

AF:

0.0161

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

163

245

326

408

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0123

Hom.:

Bravo

AF:

0.0113

Asia WGS

AF:

0.00144

AC:

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

(source)

DANN

Benign

0.82

PhyloP100

0.066

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over