5-138190059-G-T

Variant names:

• chr5-138190059-G-T
• rs17228540
• NM_004661.4:c.1425-153C>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_004661.4(CDC23):​c.1425-153C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000366 in 637,022 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0011 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: CDC23 NM_004661.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920
• Publications: 1 publications found

Genes affected

CDC23 (HGNC:1724): (cell division cycle 23) The protein encoded by this gene shares strong similarity with Saccharomyces cerevisiae Cdc23, a protein essential for cell cycle progression through the G2/M transition. This protein is a component of anaphase-promoting complex (APC), which is composed of eight protein subunits and highly conserved in eukaryotic cells. APC catalyzes the formation of cyclin B-ubiquitin conjugate that is responsible for the ubiquitin-mediated proteolysis of B-type cyclins. This protein and 3 other members of the APC complex contain the TPR (tetratricopeptide repeat), a protein domain important for protein-protein interaction. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BS2: High AC in GnomAd4 at 171 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDC23	NM_004661.4	c.1425-153C>A		intron_variant	Intron 13 of 15	ENST00000394886.7	NP_004652.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC23	ENST00000394886.7	c.1425-153C>A		intron_variant	Intron 13 of 15	1	NM_004661.4	ENSP00000378350.2
CDC23	ENST00000464806.1	n.49C>A		non_coding_transcript_exon_variant	Exon 1 of 3	2
CDC23	ENST00000475021.1	n.12C>A		non_coding_transcript_exon_variant	Exon 1 of 2	2
CDC23	ENST00000471692.1	n.943-153C>A		intron_variant	Intron 6 of 7	5

Frequencies

GnomAD3 genomes AF: 0.00112 AC: 171 AN: 152198 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00398

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000128 AC: 62 AN: 484706 Hom.: 0 Cov.: 5 AF XY: 0.0000855 AC XY: 22 AN XY: 257266

African (AFR) AF: 0.00435 AC: 56 AN: 12866

American (AMR) AF: 0.00 AC: 0 AN: 20350

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14310

East Asian (EAS) AF: 0.00 AC: 0 AN: 31600

South Asian (SAS) AF: 0.0000215 AC: 1 AN: 46524

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42382

Middle Eastern (MID) AF: 0.000462 AC: 1 AN: 2164

European-Non Finnish (NFE) AF: 0.00000696 AC: 2 AN: 287392

Other (OTH) AF: 0.0000738 AC: 2 AN: 27118

GnomAD4 genome AF: 0.00112 AC: 171 AN: 152316 Hom.: 0 Cov.: 31 AF XY: 0.000967 AC XY: 72 AN XY: 74488

African (AFR) AF: 0.00397 AC: 165 AN: 41558

American (AMR) AF: 0.000262 AC: 4 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00117

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.32
PhyloP100		-0.092

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: rs17228540; hg19: chr5-137525748;