17-65822871-A-G

Position:

• chr17-65822871-A-G

Variant summary

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

The NM_001199165.4(CEP112):​c.2394+28933T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 151,970 control chromosomes in the GnomAD database, including 42,977 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 0.75 (42977 hom., cov: 32)
• Consequence: CEP112 NM_001199165.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.733

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP112	NM_001199165.4	c.2394+28933T>C		intron_variant		ENST00000535342.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP112	ENST00000535342.7	c.2394+28933T>C		intron_variant		2	NM_001199165.4	P1

Frequencies

GnomAD3 genomes AF: 0.750 AC: 113930 AN: 151852 Hom.: 42944 Cov.: 32

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.790

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.871

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.834

Gnomad MID AF: 0.837

Gnomad NFE AF: 0.747

Gnomad OTH AF: 0.757

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

GnomAD4 genome AF: 0.750 AC: 114015 AN: 151970 Hom.: 42977 Cov.: 32 AF XY: 0.756 AC XY: 56159 AN XY: 74290

Gnomad4 AFR AF: 0.710

Gnomad4 AMR AF: 0.790

Gnomad4 ASJ AF: 0.727

Gnomad4 EAS AF: 0.870

Gnomad4 SAS AF: 0.719

Gnomad4 FIN AF: 0.834

Gnomad4 NFE AF: 0.747

Gnomad4 OTH AF: 0.760

Alfa AF: 0.750 Hom.: 36582

Bravo AF: 0.746

Asia WGS AF: 0.799 AC: 2752 AN: 3442

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.5
DANN	Benign	0.82

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: rs969981; hg19: chr17-63818989;