1-100353172-T-G

Position:

• chr1-100353172-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_003672.4(CDC14A):​c.49+169T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,168 control chromosomes in the GnomAD database, including 4,789 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.22 (4789 hom., cov: 33)
• Consequence: CDC14A NM_003672.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.01

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=-0.42).
• BP6: Variant 1-100353172-T-G is Benign according to our data. Variant chr1-100353172-T-G is described in ClinVar as [Benign]. Clinvar id is 1278440.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC14A	NM_003672.4	c.49+169T>G		intron_variant		ENST00000336454.5	NP_003663.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC14A	ENST00000336454.5	c.49+169T>G		intron_variant		1	NM_003672.4	ENSP00000336739.3

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33937 AN: 152050 Hom.: 4787 Cov.: 33

Gnomad AFR AF: 0.0537

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.223 AC: 33922 AN: 152168 Hom.: 4789 Cov.: 33 AF XY: 0.228 AC XY: 16935 AN XY: 74374

Gnomad4 AFR AF: 0.0535

Gnomad4 AMR AF: 0.218

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.405

Gnomad4 FIN AF: 0.289

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.224

Alfa AF: 0.283 Hom.: 9432

Bravo AF: 0.203

Asia WGS AF: 0.336 AC: 1166 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.42
CADD	Benign	17
DANN	Benign	0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs17420882; hg19: chr1-100818728;