17-65636955-T-C

Variant names:

• chr17-65636955-T-C
• rs2107654
• NM_001199165.4:c.2864+169A>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.2864+169A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 604,246 control chromosomes in the GnomAD database, including 73,149 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 (17763 hom., cov: 31)
  • Exomes 𝑓: 0.49 (55386 hom.)
• Consequence: CEP112 NM_001199165.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.951
• Publications: 11 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)

ENSG00000266076 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.552 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.2864+169A>G		intron	N/A	NP_001186094.1	Q8N8E3-1
	CEP112	NM_001353129.2		c.2867+169A>G		intron	N/A	NP_001340058.1
	CEP112	NM_001353127.2		c.2864+169A>G		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.2864+169A>G		intron	N/A	ENSP00000442784.2	Q8N8E3-1
	CEP112	ENST00000537949.5	TSL:1	c.2738+169A>G		intron	N/A	ENSP00000440775.1	F5GYE8
	CEP112	ENST00000317442.12	TSL:1	c.632+169A>G		intron	N/A	ENSP00000320592.5	Q8N8E3-2

Frequencies

GnomAD3 genomes AF: 0.481 AC: 72987 AN: 151630 Hom.: 17746 Cov.: 31

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.502

GnomAD4 exome AF: 0.491 AC: 222344 AN: 452494 Hom.: 55386 Cov.: 4 AF XY: 0.491 AC XY: 117515 AN XY: 239302

African (AFR) AF: 0.444 AC: 5491 AN: 12380

American (AMR) AF: 0.529 AC: 10152 AN: 19200

Ashkenazi Jewish (ASJ) AF: 0.634 AC: 8683 AN: 13704

East Asian (EAS) AF: 0.514 AC: 15899 AN: 30914

South Asian (SAS) AF: 0.492 AC: 21322 AN: 43342

European-Finnish (FIN) AF: 0.506 AC: 16650 AN: 32910

Middle Eastern (MID) AF: 0.587 AC: 1427 AN: 2432

European-Non Finnish (NFE) AF: 0.478 AC: 129818 AN: 271692

Other (OTH) AF: 0.498 AC: 12902 AN: 25920

GnomAD4 genome AF: 0.481 AC: 73033 AN: 151752 Hom.: 17763 Cov.: 31 AF XY: 0.486 AC XY: 36050 AN XY: 74170

African (AFR) AF: 0.445 AC: 18356 AN: 41272

American (AMR) AF: 0.562 AC: 8583 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.635 AC: 2202 AN: 3466

East Asian (EAS) AF: 0.463 AC: 2379 AN: 5142

South Asian (SAS) AF: 0.483 AC: 2328 AN: 4820

European-Finnish (FIN) AF: 0.510 AC: 5376 AN: 10544

Middle Eastern (MID) AF: 0.589 AC: 172 AN: 292

European-Non Finnish (NFE) AF: 0.473 AC: 32133 AN: 67934

Other (OTH) AF: 0.507 AC: 1068 AN: 2106

Alfa AF: 0.482 Hom.: 75598

Bravo AF: 0.478

Asia WGS AF: 0.510 AC: 1774 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.0
DANN	Benign	0.57
PhyloP100		0.95
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: rs2107654; hg19: chr17-63633073; COSMIC: COSV107361391; COSMIC: COSV107361391;