rs12601027

Positions:

• chr17-47126102-C-T

Variant summary

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

The NM_001256.6(CDC27):​c.2161-2142G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,144 control chromosomes in the GnomAD database, including 1,315 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 0.11 (1315 hom., cov: 32)
• Consequence: CDC27 NM_001256.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC27	NM_001256.6	c.2161-2142G>A		intron_variant		ENST00000066544.8	NP_001247.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC27	ENST00000066544.8	c.2161-2142G>A		intron_variant		1	NM_001256.6	ENSP00000066544	P5

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16432 AN: 152026 Hom.: 1320 Cov.: 32

Gnomad AFR AF: 0.0743

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.0866

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0927

Gnomad OTH AF: 0.0993

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

GnomAD4 genome AF: 0.108 AC: 16432 AN: 152144 Hom.: 1315 Cov.: 32 AF XY: 0.113 AC XY: 8411 AN XY: 74364

Gnomad4 AFR AF: 0.0742

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.0866

Gnomad4 EAS AF: 0.473

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.0927

Gnomad4 OTH AF: 0.101

Alfa AF: 0.102 Hom.: 144

Bravo AF: 0.113

Asia WGS AF: 0.236 AC: 821 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.3
DANN	Benign	0.30

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: rs12601027; hg19: chr17-45203468;