rs11570579

Variant names:

• chr17-47119930-C-T
• rs11570579
• NM_001256.6:c.*1005G>A

Variant summary

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

The NM_001256.6(CDC27):​c.*1005G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,262 control chromosomes in the GnomAD database, including 934 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 0.10 (934 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: CDC27 NM_001256.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.708
• Publications: 5 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDC27	NM_001256.6	c.*1005G>A		3_prime_UTR_variant	Exon 19 of 19	ENST00000066544.8	NP_001247.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC27	ENST00000066544.8	c.*1005G>A		3_prime_UTR_variant	Exon 19 of 19	1	NM_001256.6	ENSP00000066544.3

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15839 AN: 152144 Hom.: 934 Cov.: 32

Gnomad AFR AF: 0.0540

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.0775

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.115

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.104 AC: 15839 AN: 152262 Hom.: 934 Cov.: 32 AF XY: 0.106 AC XY: 7861 AN XY: 74448

African (AFR) AF: 0.0540 AC: 2244 AN: 41578

American (AMR) AF: 0.122 AC: 1858 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 367 AN: 3472

East Asian (EAS) AF: 0.182 AC: 944 AN: 5178

South Asian (SAS) AF: 0.201 AC: 971 AN: 4826

European-Finnish (FIN) AF: 0.0775 AC: 821 AN: 10600

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8196 AN: 67996

Other (OTH) AF: 0.114 AC: 241 AN: 2114

Alfa AF: 0.116 Hom.: 1270

Bravo AF: 0.0995

Asia WGS AF: 0.145 AC: 504 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.0
DANN	Benign	0.55
PhyloP100		0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs11570579; hg19: chr17-45197296;