17-65822871-A-G

Variant names:

• chr17-65822871-A-G
• rs969981
• NM_001199165.4:c.2394+28933T>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.2394+28933T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 151,970 control chromosomes in the GnomAD database, including 42,977 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 (42977 hom., cov: 32)
• Consequence: CEP112 NM_001199165.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.733
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.849 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP112	NM_001199165.4	MANE Select	c.2394+28933T>C		intron	N/A	NP_001186094.1
	CEP112	NM_001353129.2		c.2397+28933T>C		intron	N/A	NP_001340058.1
	CEP112	NM_001353127.2		c.2394+28933T>C		intron	N/A	NP_001340056.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP112	ENST00000535342.7	TSL:2 MANE Select	c.2394+28933T>C		intron	N/A	ENSP00000442784.2
	CEP112	ENST00000537949.5	TSL:1	c.2268+28933T>C		intron	N/A	ENSP00000440775.1
	CEP112	ENST00000317442.12	TSL:1	c.162+3267T>C		intron	N/A	ENSP00000320592.5

Frequencies

GnomAD3 genomes AF: 0.750 AC: 113930 AN: 151852 Hom.: 42944 Cov.: 32

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.790

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.871

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.834

Gnomad MID AF: 0.837

Gnomad NFE AF: 0.747

Gnomad OTH AF: 0.757

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

GnomAD4 genome AF: 0.750 AC: 114015 AN: 151970 Hom.: 42977 Cov.: 32 AF XY: 0.756 AC XY: 56159 AN XY: 74290

African (AFR) AF: 0.710 AC: 29417 AN: 41444

American (AMR) AF: 0.790 AC: 12070 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.727 AC: 2524 AN: 3470

East Asian (EAS) AF: 0.870 AC: 4505 AN: 5176

South Asian (SAS) AF: 0.719 AC: 3474 AN: 4832

European-Finnish (FIN) AF: 0.834 AC: 8811 AN: 10560

Middle Eastern (MID) AF: 0.841 AC: 244 AN: 290

European-Non Finnish (NFE) AF: 0.747 AC: 50716 AN: 67910

Other (OTH) AF: 0.760 AC: 1600 AN: 2104

Alfa AF: 0.749 Hom.: 42637

Bravo AF: 0.746

Asia WGS AF: 0.799 AC: 2752 AN: 3442

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.5
DANN	Benign	0.82
PhyloP100		0.73
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: rs969981; hg19: chr17-63818989;