17-65659263-C-T

Variant names:

• chr17-65659263-C-T
• rs9889486
• NM_001199165.4:c.2698-18198G>A

Variant summary

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

The NM_001199165.4(CEP112):​c.2698-18198G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 151,928 control chromosomes in the GnomAD database, including 23,586 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 0.55 (23586 hom., cov: 31)
• Consequence: CEP112 NM_001199165.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.745
• Publications: 3 publications found

Genes affected

CEP112 (HGNC:28514): (centrosomal protein 112) This gene encodes a coiled-coil domain containing protein that belongs to the cell division control protein 42 effector protein family. In neurons, it localizes to the cytoplasm of dendrites and is also enriched in the nucleus where it interacts with the RNA polymerase III transcriptional repressor Maf1 to regulate gamma-aminobutyric acid A receptor surface expression. In addition, the protein has been identified as a component of the human centrosome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]

CEP112 Gene-Disease associations (from GenCC):

• spermatogenic failure 44

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP112	NM_001199165.4	c.2698-18198G>A		intron_variant	Intron 24 of 26	ENST00000535342.7	NP_001186094.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP112	ENST00000535342.7	c.2698-18198G>A		intron_variant	Intron 24 of 26	2	NM_001199165.4	ENSP00000442784.2

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83180 AN: 151810 Hom.: 23550 Cov.: 31

Gnomad AFR AF: 0.677

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.764

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.527

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

GnomAD4 genome AF: 0.548 AC: 83272 AN: 151928 Hom.: 23586 Cov.: 31 AF XY: 0.548 AC XY: 40657 AN XY: 74240

African (AFR) AF: 0.677 AC: 28044 AN: 41400

American (AMR) AF: 0.532 AC: 8117 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 1718 AN: 3466

East Asian (EAS) AF: 0.764 AC: 3957 AN: 5178

South Asian (SAS) AF: 0.471 AC: 2262 AN: 4804

European-Finnish (FIN) AF: 0.501 AC: 5277 AN: 10526

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.473 AC: 32139 AN: 67970

Other (OTH) AF: 0.531 AC: 1122 AN: 2112

Alfa AF: 0.499 Hom.: 27695

Bravo AF: 0.563

Asia WGS AF: 0.623 AC: 2164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	13
DANN	Benign	0.64
PhyloP100		0.74
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: rs9889486; hg19: chr17-63655381;