chr17-66102427-T-C

Variant names:

• chr17-66102427-T-C
• rs2319125
• NM_001199165.4:c.643-5795A>G

Variant summary

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

The NM_001199165.4(CEP112):​c.643-5795A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 151,914 control chromosomes in the GnomAD database, including 10,451 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 0.34 (10451 hom., cov: 32)
• Consequence: CEP112 NM_001199165.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.908
• Publications: 5 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 (NFE) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP112	NM_001199165.4	c.643-5795A>G		intron_variant	Intron 6 of 26	ENST00000535342.7	NP_001186094.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP112	ENST00000535342.7	c.643-5795A>G		intron_variant	Intron 6 of 26	2	NM_001199165.4	ENSP00000442784.2

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51634 AN: 151796 Hom.: 10453 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.0434

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.349

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

GnomAD4 genome AF: 0.340 AC: 51624 AN: 151914 Hom.: 10451 Cov.: 32 AF XY: 0.338 AC XY: 25071 AN XY: 74236

African (AFR) AF: 0.167 AC: 6922 AN: 41468

American (AMR) AF: 0.286 AC: 4361 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1201 AN: 3470

East Asian (EAS) AF: 0.0435 AC: 225 AN: 5174

South Asian (SAS) AF: 0.232 AC: 1117 AN: 4818

European-Finnish (FIN) AF: 0.526 AC: 5517 AN: 10480

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.458 AC: 31126 AN: 67938

Other (OTH) AF: 0.344 AC: 726 AN: 2110

Alfa AF: 0.342 Hom.: 5039

Bravo AF: 0.312

Asia WGS AF: 0.136 AC: 470 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.88
DANN	Benign	0.60
PhyloP100		-0.91
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: rs2319125; hg19: chr17-64098545;