rs701982

Variant names:

• chr17-47167456-T-G
• rs701982
• NM_001256.6:c.377+2461A>C

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.285
• Publications: 2 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]

ENSG00000262265 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CDC27	NM_001256.6	c.377+2461A>C		intron_variant	Intron 4 of 18	ENST00000066544.8	NP_001247.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC27	ENST00000066544.8	c.377+2461A>C		intron_variant	Intron 4 of 18	1	NM_001256.6	ENSP00000066544.3

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66527 AN: 151800 Hom.: 15240 Cov.: 31

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

African (AFR) AF: 0.363 AC: 15035 AN: 41396

American (AMR) AF: 0.515 AC: 7863 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1553 AN: 3468

East Asian (EAS) AF: 0.149 AC: 773 AN: 5176

South Asian (SAS) AF: 0.282 AC: 1361 AN: 4818

European-Finnish (FIN) AF: 0.457 AC: 4811 AN: 10524

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.494 AC: 33552 AN: 67974

Other (OTH) AF: 0.469 AC: 988 AN: 2106

Alfa AF: 0.473 Hom.: 15620

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
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs701982; hg19: chr17-45244822;