rs997651

Positions:

• chr17-65918265-G-A
• chr17-65918265-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001199165.4(CEP112):​c.1980+9317C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 151,540 control chromosomes in the GnomAD database, including 13,337 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 (13337 hom., cov: 31)
• Consequence: CEP112 NM_001199165.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.558

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP112	NM_001199165.4	c.1980+9317C>T		intron_variant		ENST00000535342.7	NP_001186094.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP112	ENST00000535342.7	c.1980+9317C>T		intron_variant		2	NM_001199165.4	ENSP00000442784	P1

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62466 AN: 151422 Hom.: 13307 Cov.: 31

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.649

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.437

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

GnomAD4 genome AF: 0.413 AC: 62543 AN: 151540 Hom.: 13337 Cov.: 31 AF XY: 0.415 AC XY: 30709 AN XY: 74016

Gnomad4 AFR AF: 0.458

Gnomad4 AMR AF: 0.473

Gnomad4 ASJ AF: 0.469

Gnomad4 EAS AF: 0.193

Gnomad4 SAS AF: 0.648

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.390

Gnomad4 OTH AF: 0.437

Alfa AF: 0.408 Hom.: 6033

Bravo AF: 0.419

Asia WGS AF: 0.436 AC: 1515 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.57
DANN	Benign	0.56

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: rs997651; hg19: chr17-63914383;