rs2241008

Variant names:

• chr17-65902039-C-T
• rs2241008
• NM_001199165.4:c.2163+113G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001199165.4(CEP112):​c.2163+113G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 418,364 control chromosomes in the GnomAD database, including 133,357 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 0.75 (38740 hom., cov: 20)
  • Exomes 𝑓: 0.81 (94617 hom.)
• Consequence: CEP112 NM_001199165.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.25
• 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)

LOC105371867 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199165.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP112	NM_001199165.4	MANE Select	c.2163+113G>A		intron	N/A	NP_001186094.1	Q8N8E3-1
	CEP112	NM_001353129.2		c.2166+113G>A		intron	N/A	NP_001340058.1
	CEP112	NM_001353127.2		c.2163+113G>A		intron	N/A	NP_001340056.1	Q8N8E3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP112	ENST00000535342.7	TSL:2 MANE Select	c.2163+113G>A		intron	N/A	ENSP00000442784.2	Q8N8E3-1
	CEP112	ENST00000537949.5	TSL:1	c.2037+113G>A		intron	N/A	ENSP00000440775.1	F5GYE8
	CEP112	ENST00000859226.1		c.2262+113G>A		intron	N/A	ENSP00000529285.1

Frequencies

GnomAD3 genomes AF: 0.749 AC: 98916 AN: 132140 Hom.: 38730 Cov.: 20

Gnomad AFR AF: 0.555

Gnomad AMI AF: 0.880

Gnomad AMR AF: 0.765

Gnomad ASJ AF: 0.839

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.800

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.873

Gnomad OTH AF: 0.769

GnomAD4 exome AF: 0.805 AC: 230374 AN: 286126 Hom.: 94617 AF XY: 0.808 AC XY: 121070 AN XY: 149832

African (AFR) AF: 0.599 AC: 4341 AN: 7248

American (AMR) AF: 0.726 AC: 6184 AN: 8520

Ashkenazi Jewish (ASJ) AF: 0.836 AC: 7312 AN: 8748

East Asian (EAS) AF: 0.321 AC: 4987 AN: 15526

South Asian (SAS) AF: 0.788 AC: 9925 AN: 12596

European-Finnish (FIN) AF: 0.711 AC: 16474 AN: 23172

Middle Eastern (MID) AF: 0.841 AC: 1179 AN: 1402

European-Non Finnish (NFE) AF: 0.867 AC: 166737 AN: 192276

Other (OTH) AF: 0.795 AC: 13235 AN: 16638

GnomAD4 genome AF: 0.748 AC: 98969 AN: 132238 Hom.: 38740 Cov.: 20 AF XY: 0.739 AC XY: 46056 AN XY: 62348

African (AFR) AF: 0.555 AC: 19364 AN: 34880

American (AMR) AF: 0.764 AC: 8547 AN: 11180

Ashkenazi Jewish (ASJ) AF: 0.839 AC: 2832 AN: 3374

East Asian (EAS) AF: 0.280 AC: 1125 AN: 4018

South Asian (SAS) AF: 0.800 AC: 3115 AN: 3894

European-Finnish (FIN) AF: 0.691 AC: 4572 AN: 6616

Middle Eastern (MID) AF: 0.858 AC: 206 AN: 240

European-Non Finnish (NFE) AF: 0.873 AC: 57040 AN: 65334

Other (OTH) AF: 0.765 AC: 1392 AN: 1820

Alfa AF: 0.850 Hom.: 79018

Bravo AF: 0.730

Asia WGS AF: 0.549 AC: 1903 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	21
DANN	Benign	0.87
PhyloP100		3.3
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: rs2241008; hg19: chr17-63898157;