rs2107654

Positions:

• chr17-65636955-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ENSG00000266076 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP112	NM_001199165.4	c.2864+169A>G		intron_variant		ENST00000535342.7	NP_001186094.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP112	ENST00000535342.7	c.2864+169A>G		intron_variant		2	NM_001199165.4	ENSP00000442784.2
ENSG00000266076	ENST00000577662.1	n.134+169A>G		intron_variant		2		ENSP00000462418.1

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

Gnomad4 AFR exome AF: 0.444

Gnomad4 AMR exome AF: 0.529

Gnomad4 ASJ exome AF: 0.634

Gnomad4 EAS exome AF: 0.514

Gnomad4 SAS exome AF: 0.492

Gnomad4 FIN exome AF: 0.506

Gnomad4 NFE exome AF: 0.478

Gnomad4 OTH exome AF: 0.498

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

Gnomad4 AFR AF: 0.445

Gnomad4 AMR AF: 0.562

Gnomad4 ASJ AF: 0.635

Gnomad4 EAS AF: 0.463

Gnomad4 SAS AF: 0.483

Gnomad4 FIN AF: 0.510

Gnomad4 NFE AF: 0.473

Gnomad4 OTH AF: 0.507

Alfa AF: 0.488 Hom.: 37496

Bravo AF: 0.478

Asia WGS AF: 0.510 AC: 1774 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.0
DANN	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs2107654; hg19: chr17-63633073;