rs16941635

Variant names:

• chr17-47184589-G-A
• rs16941635
• NM_001256.6:c.28-2952C>T

Variant summary

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

The NM_001256.6(CDC27):​c.28-2952C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.079 in 152,230 control chromosomes in the GnomAD database, including 638 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 0.079 (638 hom., cov: 32)
• Consequence: CDC27 NM_001256.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.255
• Publications: 6 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 = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDC27	NM_001256.6	c.28-2952C>T		intron_variant	Intron 1 of 18	ENST00000066544.8	NP_001247.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC27	ENST00000066544.8	c.28-2952C>T		intron_variant	Intron 1 of 18	1	NM_001256.6	ENSP00000066544.3

Frequencies

GnomAD3 genomes AF: 0.0791 AC: 12026 AN: 152112 Hom.: 638 Cov.: 32

Gnomad AFR AF: 0.0250

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.0911

Gnomad ASJ AF: 0.0809

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.0690

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0948

Gnomad OTH AF: 0.0781

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

GnomAD4 genome AF: 0.0790 AC: 12025 AN: 152230 Hom.: 638 Cov.: 32 AF XY: 0.0819 AC XY: 6097 AN XY: 74430

African (AFR) AF: 0.0249 AC: 1036 AN: 41558

American (AMR) AF: 0.0911 AC: 1392 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0809 AC: 281 AN: 3472

East Asian (EAS) AF: 0.182 AC: 943 AN: 5184

South Asian (SAS) AF: 0.186 AC: 898 AN: 4824

European-Finnish (FIN) AF: 0.0690 AC: 731 AN: 10592

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0948 AC: 6446 AN: 68002

Other (OTH) AF: 0.0777 AC: 164 AN: 2110

Alfa AF: 0.0937 Hom.: 961

Bravo AF: 0.0732

Asia WGS AF: 0.141 AC: 493 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.44
DANN	Benign	0.74
PhyloP100		-0.26
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: rs16941635; hg19: chr17-45261955;