1-100352730-A-T

Position:

• chr1-100352730-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003672.4(CDC14A):​c.-225A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.906 in 1,390,688 control chromosomes in the GnomAD database, including 574,133 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.84 (54516 hom., cov: 34)
  • Exomes 𝑓: 0.91 (519617 hom.)
• Consequence: CDC14A NM_003672.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.578

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 1-100352730-A-T is Benign according to our data. Variant chr1-100352730-A-T is described in ClinVar as [Benign]. Clinvar id is 1294730.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC14A	NM_003672.4	c.-225A>T		5_prime_UTR_variant	1/16	ENST00000336454.5	NP_003663.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC14A	ENST00000336454.5	c.-225A>T		5_prime_UTR_variant	1/16	1	NM_003672.4	ENSP00000336739.3

Frequencies

GnomAD3 genomes AF: 0.836 AC: 127194 AN: 152058 Hom.: 54491 Cov.: 34

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.933

Gnomad AMR AF: 0.859

Gnomad ASJ AF: 0.929

Gnomad EAS AF: 0.930

Gnomad SAS AF: 0.859

Gnomad FIN AF: 0.933

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.926

Gnomad OTH AF: 0.850

GnomAD4 exome AF: 0.915 AC: 1132809 AN: 1238512 Hom.: 519617 Cov.: 57 AF XY: 0.914 AC XY: 548000 AN XY: 599424

Gnomad4 AFR exome AF: 0.625

Gnomad4 AMR exome AF: 0.859

Gnomad4 ASJ exome AF: 0.924

Gnomad4 EAS exome AF: 0.932

Gnomad4 SAS exome AF: 0.867

Gnomad4 FIN exome AF: 0.933

Gnomad4 NFE exome AF: 0.925

Gnomad4 OTH exome AF: 0.902

GnomAD4 genome AF: 0.836 AC: 127264 AN: 152176 Hom.: 54516 Cov.: 34 AF XY: 0.837 AC XY: 62285 AN XY: 74410

Gnomad4 AFR AF: 0.631

Gnomad4 AMR AF: 0.858

Gnomad4 ASJ AF: 0.929

Gnomad4 EAS AF: 0.931

Gnomad4 SAS AF: 0.859

Gnomad4 FIN AF: 0.933

Gnomad4 NFE AF: 0.926

Gnomad4 OTH AF: 0.849

Alfa AF: 0.870 Hom.: 3027

Bravo AF: 0.825

Asia WGS AF: 0.874 AC: 3037 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	16
DANN	Benign	0.87

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

Publications

LitVar

Other links and lift over

dbSNP: rs527644; hg19: chr1-100818286;