rs8074751

Variant names:

• chr17-65646424-G-A
• rs8074751
• NM_001199165.4:c.2698-5359C>T

Variant summary

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

The NM_001199165.4(CEP112):​c.2698-5359C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.697 in 152,102 control chromosomes in the GnomAD database, including 38,532 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 0.70 (38532 hom., cov: 32)
• Consequence: CEP112 NM_001199165.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.287
• Publications: 11 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.927 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP112	NM_001199165.4	c.2698-5359C>T		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.2698-5359C>T		intron_variant	Intron 24 of 26	2	NM_001199165.4	ENSP00000442784.2

Frequencies

GnomAD3 genomes AF: 0.697 AC: 105980 AN: 151984 Hom.: 38476 Cov.: 32

Gnomad AFR AF: 0.885

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.949

Gnomad SAS AF: 0.611

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.679

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

GnomAD4 genome AF: 0.697 AC: 106089 AN: 152102 Hom.: 38532 Cov.: 32 AF XY: 0.701 AC XY: 52077 AN XY: 74340

African (AFR) AF: 0.885 AC: 36749 AN: 41526

American (AMR) AF: 0.741 AC: 11325 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.659 AC: 2287 AN: 3472

East Asian (EAS) AF: 0.949 AC: 4911 AN: 5174

South Asian (SAS) AF: 0.610 AC: 2942 AN: 4822

European-Finnish (FIN) AF: 0.617 AC: 6509 AN: 10548

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.576 AC: 39183 AN: 67968

Other (OTH) AF: 0.680 AC: 1437 AN: 2112

Alfa AF: 0.628 Hom.: 73116

Bravo AF: 0.718

Asia WGS AF: 0.791 AC: 2748 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.7
DANN	Benign	0.33
PhyloP100		0.29
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: rs8074751; hg19: chr17-63642542;