rs614805

Variant names:

• chr1-100331917-T-C
• rs614805
• ENST00000401024.2:n.701A>G

Variant summary

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

The ENST00000401024.2(ENSG00000215871):​n.701A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 1,071,492 control chromosomes in the GnomAD database, including 164,979 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 0.62 (31621 hom., cov: 33)
  • Exomes 𝑓: 0.53 (133358 hom.)
• Consequence: ENSG00000215871 ENST00000401024.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.920
• Publications: 3 publications found

Genes affected

ENSG00000215871 (HGNC:58661):

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

ENSG00000300501 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.893 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C5orf15P1		n.100331917T>C		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000215871	ENST00000401024.2	n.701A>G		non_coding_transcript_exon_variant	Exon 1 of 1	6
CDC14A	ENST00000717967.1	c.70+6064T>C		intron_variant	Intron 1 of 15			ENSP00000520653.1
ENSG00000300501	ENST00000772398.1	n.*85A>G		downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.619 AC: 94114 AN: 151980 Hom.: 31571 Cov.: 33

Gnomad AFR AF: 0.901

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.608

GnomAD4 exome AF: 0.532 AC: 489104 AN: 919394 Hom.: 133358 Cov.: 13 AF XY: 0.532 AC XY: 255008 AN XY: 479120

African (AFR) AF: 0.907 AC: 20094 AN: 22158

American (AMR) AF: 0.421 AC: 16469 AN: 39144

Ashkenazi Jewish (ASJ) AF: 0.521 AC: 11363 AN: 21806

East Asian (EAS) AF: 0.454 AC: 16815 AN: 37042

South Asian (SAS) AF: 0.584 AC: 41430 AN: 70996

European-Finnish (FIN) AF: 0.510 AC: 26487 AN: 51980

Middle Eastern (MID) AF: 0.568 AC: 1803 AN: 3172

European-Non Finnish (NFE) AF: 0.525 AC: 331499 AN: 631318

Other (OTH) AF: 0.554 AC: 23144 AN: 41778

GnomAD4 genome AF: 0.619 AC: 94212 AN: 152098 Hom.: 31621 Cov.: 33 AF XY: 0.617 AC XY: 45825 AN XY: 74326

African (AFR) AF: 0.901 AC: 37418 AN: 41528

American (AMR) AF: 0.490 AC: 7492 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.509 AC: 1765 AN: 3470

East Asian (EAS) AF: 0.449 AC: 2326 AN: 5178

South Asian (SAS) AF: 0.591 AC: 2851 AN: 4826

European-Finnish (FIN) AF: 0.514 AC: 5425 AN: 10546

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.514 AC: 34934 AN: 67962

Other (OTH) AF: 0.615 AC: 1298 AN: 2112

Alfa AF: 0.569 Hom.: 11158

Bravo AF: 0.626

Asia WGS AF: 0.573 AC: 1998 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.1
DANN	Benign	0.84
PhyloP100		0.92

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs614805; hg19: chr1-100797473;