17-65769793-T-G

Variant names:

• chr17-65769793-T-G
• rs987931
• NM_001199165.4:c.2395-19069A>C

Variant summary

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

The NM_001199165.4(CEP112):​c.2395-19069A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 151,854 control chromosomes in the GnomAD database, including 20,049 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 0.49 (20049 hom., cov: 32)
• Consequence: CEP112 NM_001199165.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 2 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP112	NM_001199165.4	c.2395-19069A>C		intron_variant	Intron 21 of 26	ENST00000535342.7	NP_001186094.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP112	ENST00000535342.7	c.2395-19069A>C		intron_variant	Intron 21 of 26	2	NM_001199165.4	ENSP00000442784.2

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74029 AN: 151736 Hom.: 20010 Cov.: 32

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.804

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.471

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

GnomAD4 genome AF: 0.488 AC: 74123 AN: 151854 Hom.: 20049 Cov.: 32 AF XY: 0.492 AC XY: 36496 AN XY: 74230

African (AFR) AF: 0.699 AC: 28980 AN: 41436

American (AMR) AF: 0.516 AC: 7871 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1125 AN: 3470

East Asian (EAS) AF: 0.804 AC: 4156 AN: 5170

South Asian (SAS) AF: 0.531 AC: 2553 AN: 4810

European-Finnish (FIN) AF: 0.363 AC: 3838 AN: 10564

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.356 AC: 24185 AN: 67850

Other (OTH) AF: 0.468 AC: 988 AN: 2110

Alfa AF: 0.440 Hom.: 2079

Bravo AF: 0.508

Asia WGS AF: 0.656 AC: 2278 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.35
DANN	Benign	0.81
PhyloP100		-1.0
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: rs987931; hg19: chr17-63765911;