chr1-100353172-T-G

Variant names:

• chr1-100353172-T-G
• rs17420882
• NM_003672.4:c.49+169T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 publications found

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]

CDC14A Gene-Disease associations (from GenCC):

• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive nonsyndromic deafness 105

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• hearing impairment and infertile male syndrome

  Inheritance: AR Classification: STRONG Submitted by: ClinGen
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal recessive nonsyndromic hearing loss 32

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003672.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC14A	NM_003672.4	MANE Select	c.49+169T>G		intron	N/A	NP_003663.2
	CDC14A	NM_033312.3		c.49+169T>G		intron	N/A	NP_201569.1	Q9UNH5-2
	CDC14A	NM_001319210.2		c.49+169T>G		intron	N/A	NP_001306139.1	Q9UNH5-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC14A	ENST00000336454.5	TSL:1 MANE Select	c.49+169T>G		intron	N/A	ENSP00000336739.3	Q9UNH5-1
	CDC14A	ENST00000361544.11	TSL:1	c.49+169T>G		intron	N/A	ENSP00000354916.6	Q9UNH5-2
	CDC14A	ENST00000370124.8	TSL:1	c.49+169T>G		intron	N/A	ENSP00000359142.3	Q9UNH5-3

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

African (AFR) AF: 0.0535 AC: 2224 AN: 41552

American (AMR) AF: 0.218 AC: 3331 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 997 AN: 3470

East Asian (EAS) AF: 0.332 AC: 1710 AN: 5150

South Asian (SAS) AF: 0.405 AC: 1953 AN: 4822

European-Finnish (FIN) AF: 0.289 AC: 3061 AN: 10592

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.292 AC: 19835 AN: 67976

Other (OTH) AF: 0.224 AC: 473 AN: 2112

Alfa AF: 0.274 Hom.: 13266

Bravo AF: 0.203

Asia WGS AF: 0.336 AC: 1166 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	17
DANN	Benign	0.76
PhyloP100		1.0
PromoterAI		-0.081	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs17420882; hg19: chr1-100818728;