17-65918247-G-T

Variant names:

• chr17-65918247-G-T
• rs997652
• NM_001199165.4:c.1980+9335C>A

Variant summary

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

The NM_001199165.4(CEP112):​c.1980+9335C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 151,274 control chromosomes in the GnomAD database, including 13,290 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 0.41 (13290 hom., cov: 30)
• Consequence: CEP112 NM_001199165.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.629 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.1980+9335C>A		intron	N/A	NP_001186094.1	Q8N8E3-1
	CEP112	NM_001353129.2		c.1983+9335C>A		intron	N/A	NP_001340058.1
	CEP112	NM_001353127.2		c.1980+9335C>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.1980+9335C>A		intron	N/A	ENSP00000442784.2	Q8N8E3-1
	CEP112	ENST00000537949.5	TSL:1	c.1854+9335C>A		intron	N/A	ENSP00000440775.1	F5GYE8
	CEP112	ENST00000859226.1		c.2079+9335C>A		intron	N/A	ENSP00000529285.1

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62275 AN: 151156 Hom.: 13261 Cov.: 30

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.436

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

GnomAD4 genome AF: 0.412 AC: 62350 AN: 151274 Hom.: 13290 Cov.: 30 AF XY: 0.414 AC XY: 30587 AN XY: 73840

African (AFR) AF: 0.457 AC: 18821 AN: 41152

American (AMR) AF: 0.472 AC: 7171 AN: 15180

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 1627 AN: 3462

East Asian (EAS) AF: 0.192 AC: 990 AN: 5156

South Asian (SAS) AF: 0.648 AC: 3111 AN: 4804

European-Finnish (FIN) AF: 0.277 AC: 2869 AN: 10376

Middle Eastern (MID) AF: 0.425 AC: 124 AN: 292

European-Non Finnish (NFE) AF: 0.389 AC: 26411 AN: 67846

Other (OTH) AF: 0.435 AC: 915 AN: 2102

Alfa AF: 0.382 Hom.: 1342

Bravo AF: 0.419

Asia WGS AF: 0.435 AC: 1513 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.14
DANN	Benign	0.47
PhyloP100		-1.6
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: rs997652; hg19: chr17-63914365;