17-65852037-T-A

Position:

• chr17-65852037-T-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001199165.4(CEP112):​c.2164-3A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,594,824 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00071 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (4 hom.)
• Consequence: CEP112 NM_001199165.4 splice_region, intron
• Scores: Splicing: ADA: 0.0001285
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.184

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 17-65852037-T-A is Benign according to our data. Variant chr17-65852037-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 2648109.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP112	NM_001199165.4	c.2164-3A>T		splice_region_variant, intron_variant		ENST00000535342.7	NP_001186094.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP112	ENST00000535342.7	c.2164-3A>T		splice_region_variant, intron_variant		2	NM_001199165.4	ENSP00000442784.2

Frequencies

GnomAD3 genomes AF: 0.000710 AC: 108 AN: 152198 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000289

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00122

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000780 AC: 181 AN: 232060 Hom.: 1 AF XY: 0.000740 AC XY: 93 AN XY: 125662

Gnomad AFR exome AF: 0.000189

Gnomad AMR exome AF: 0.000300

Gnomad ASJ exome AF: 0.000114

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000566

Gnomad FIN exome AF: 0.000252

Gnomad NFE exome AF: 0.00133

Gnomad OTH exome AF: 0.000717

GnomAD4 exome AF: 0.00106 AC: 1535 AN: 1442508 Hom.: 4 Cov.: 30 AF XY: 0.00104 AC XY: 743 AN XY: 717086

Gnomad4 AFR exome AF: 0.000155

Gnomad4 AMR exome AF: 0.000248

Gnomad4 ASJ exome AF: 0.000199

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000543

Gnomad4 FIN exome AF: 0.000137

Gnomad4 NFE exome AF: 0.00129

Gnomad4 OTH exome AF: 0.000672

GnomAD4 genome AF: 0.000709 AC: 108 AN: 152316 Hom.: 0 Cov.: 32 AF XY: 0.000564 AC XY: 42 AN XY: 74482

Gnomad4 AFR AF: 0.000289

Gnomad4 AMR AF: 0.000392

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00122

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000738 Hom.: 0

Bravo AF: 0.000688

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2023

CEP112: BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.5
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00013
dbscSNV1_RF	Benign	0.032
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: rs201042942; hg19: chr17-63848155;