17-65947838-A-G

Variant names:

• chr17-65947838-A-G
• rs1990743
• NM_001199165.4:c.1872+13625T>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.1872+13625T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 151,842 control chromosomes in the GnomAD database, including 18,386 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 0.48 (18386 hom., cov: 32)
• Consequence: CEP112 NM_001199165.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.165
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP112	NM_001199165.4	c.1872+13625T>C		intron_variant	Intron 18 of 26	ENST00000535342.7	NP_001186094.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP112	ENST00000535342.7	c.1872+13625T>C		intron_variant	Intron 18 of 26	2	NM_001199165.4	ENSP00000442784.2

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72596 AN: 151726 Hom.: 18355 Cov.: 32

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.894

Gnomad SAS AF: 0.736

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.455

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.507

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

GnomAD4 genome AF: 0.479 AC: 72673 AN: 151842 Hom.: 18386 Cov.: 32 AF XY: 0.488 AC XY: 36251 AN XY: 74220

African (AFR) AF: 0.397 AC: 16452 AN: 41430

American (AMR) AF: 0.632 AC: 9648 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1854 AN: 3468

East Asian (EAS) AF: 0.893 AC: 4621 AN: 5172

South Asian (SAS) AF: 0.738 AC: 3535 AN: 4792

European-Finnish (FIN) AF: 0.420 AC: 4433 AN: 10550

Middle Eastern (MID) AF: 0.455 AC: 133 AN: 292

European-Non Finnish (NFE) AF: 0.449 AC: 30495 AN: 67860

Other (OTH) AF: 0.513 AC: 1078 AN: 2102

Alfa AF: 0.316 Hom.: 1006

Bravo AF: 0.490

Asia WGS AF: 0.780 AC: 2699 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.8
DANN	Benign	0.60
PhyloP100		-0.17
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: rs1990743; hg19: chr17-63943956;