rs701982

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001256.6(CDC27):​c.377+2461A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 151,920 control chromosomes in the GnomAD database, including 15,246 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 0.44 ( 15246 hom., cov: 31)

Consequence

CDC27
NM_001256.6 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.285
Variant links:
Genes affected
CDC27 (HGNC:1728): (cell division cycle 27) The protein encoded by this gene shares strong similarity with Saccharomyces cerevisiae protein Cdc27, and the gene product of Schizosaccharomyces pombe nuc 2. This protein is a component of the anaphase-promoting complex (APC), which is composed of eight protein subunits and is highly conserved in eukaryotic cells. This complex catalyzes the formation of cyclin B-ubiquitin conjugate, which is responsible for the ubiquitin-mediated proteolysis of B-type cyclins. The protein encoded by this gene and three other members of the APC complex contain tetratricopeptide (TPR) repeats, which are important for protein-protein interactions. This protein was shown to interact with mitotic checkpoint proteins including Mad2, p55CDC and BUBR1, and it may thus be involved in controlling the timing of mitosis. Alternative splicing of this gene results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 2, 22 and Y. [provided by RefSeq, May 2014]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CDC27NM_001256.6 linkuse as main transcriptc.377+2461A>C intron_variant ENST00000066544.8 NP_001247.3 P30260-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CDC27ENST00000066544.8 linkuse as main transcriptc.377+2461A>C intron_variant 1 NM_001256.6 ENSP00000066544.3 P30260-1

Frequencies

GnomAD3 genomes
AF:
0.438
AC:
66527
AN:
151800
Hom.:
15240
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.363
Gnomad AMI
AF:
0.513
Gnomad AMR
AF:
0.515
Gnomad ASJ
AF:
0.448
Gnomad EAS
AF:
0.149
Gnomad SAS
AF:
0.284
Gnomad FIN
AF:
0.457
Gnomad MID
AF:
0.547
Gnomad NFE
AF:
0.494
Gnomad OTH
AF:
0.468
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.438
AC:
66563
AN:
151920
Hom.:
15246
Cov.:
31
AF XY:
0.432
AC XY:
32040
AN XY:
74214
show subpopulations
Gnomad4 AFR
AF:
0.363
Gnomad4 AMR
AF:
0.515
Gnomad4 ASJ
AF:
0.448
Gnomad4 EAS
AF:
0.149
Gnomad4 SAS
AF:
0.282
Gnomad4 FIN
AF:
0.457
Gnomad4 NFE
AF:
0.494
Gnomad4 OTH
AF:
0.469
Alfa
AF:
0.470
Hom.:
11118
Bravo
AF:
0.439
Asia WGS
AF:
0.294
AC:
1022
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
1.1
DANN
Benign
0.75

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs701982; hg19: chr17-45244822; API