1-100490922-A-G

Variant names:

• chr1-100490922-A-G
• rs12722868
• NM_003672.4:c.1138-3896A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003672.4(CDC14A):​c.1138-3896A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 152,078 control chromosomes in the GnomAD database, including 8,720 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 0.31 (8720 hom., cov: 32)
• Consequence: CDC14A NM_003672.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0280
• Publications: 6 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):

• autosomal recessive nonsyndromic deafness 105

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• autosomal recessive nonsyndromic hearing loss 32

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, PanelApp Australia
• hearing impairment and infertile male syndrome

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ENSG00000228086 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDC14A	NM_003672.4	c.1138-3896A>G		intron_variant	Intron 11 of 15	ENST00000336454.5	NP_003663.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC14A	ENST00000336454.5	c.1138-3896A>G		intron_variant	Intron 11 of 15	1	NM_003672.4	ENSP00000336739.3

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47650 AN: 151960 Hom.: 8717 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.488

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.313 AC: 47653 AN: 152078 Hom.: 8720 Cov.: 32 AF XY: 0.317 AC XY: 23533 AN XY: 74330

African (AFR) AF: 0.113 AC: 4671 AN: 41494

American (AMR) AF: 0.413 AC: 6308 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1149 AN: 3470

East Asian (EAS) AF: 0.489 AC: 2531 AN: 5176

South Asian (SAS) AF: 0.403 AC: 1941 AN: 4818

European-Finnish (FIN) AF: 0.358 AC: 3777 AN: 10550

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.385 AC: 26160 AN: 67974

Other (OTH) AF: 0.317 AC: 670 AN: 2112

Alfa AF: 0.374 Hom.: 5847

Bravo AF: 0.309

Asia WGS AF: 0.398 AC: 1382 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.9
DANN	Benign	0.41
PhyloP100		0.028
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: rs12722868; hg19: chr1-100956478;