rs508020

Positions:

• chr1-100489976-T-C

Variant summary

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

The NM_003672.4(CDC14A):​c.1138-4842T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 152,028 control chromosomes in the GnomAD database, including 13,592 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 0.41 (13592 hom., cov: 31)
• Consequence: CDC14A NM_003672.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.167

Genes affected

CDC14A (HGNC:1718): (cell division cycle 14A) The protein encoded by this gene is a member of the dual specificity protein tyrosine phosphatase family. It is highly similar to Saccharomyces cerevisiae Cdc14, a protein tyrosine phosphatase involved in the exit of cell mitosis and initiation of DNA replication, suggesting a role in cell cycle control. This protein has been shown to interact with, and dephosphorylate tumor suppressor protein p53, and is thought to regulate the function of p53. Alternative splicing of this gene results in several transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDC14A	NM_003672.4	c.1138-4842T>C		intron_variant		ENST00000336454.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDC14A	ENST00000336454.5	c.1138-4842T>C		intron_variant		1	NM_003672.4	A1

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62735 AN: 151910 Hom.: 13595 Cov.: 31

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.427

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

GnomAD4 genome AF: 0.413 AC: 62743 AN: 152028 Hom.: 13592 Cov.: 31 AF XY: 0.412 AC XY: 30609 AN XY: 74356

Gnomad4 AFR AF: 0.288

Gnomad4 AMR AF: 0.398

Gnomad4 ASJ AF: 0.450

Gnomad4 EAS AF: 0.372

Gnomad4 SAS AF: 0.484

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.478

Gnomad4 OTH AF: 0.427

Alfa AF: 0.461 Hom.: 27875

Bravo AF: 0.401

Asia WGS AF: 0.415 AC: 1445 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.8
DANN	Benign	0.74

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: rs508020; hg19: chr1-100955532;