chr17-66137608-T-C

Variant names:

• chr17-66137608-T-C
• rs7209395
• NM_001199165.4:c.471-4845A>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.471-4845A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,088 control chromosomes in the GnomAD database, including 3,721 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 0.21 (3721 hom., cov: 32)
• Consequence: CEP112 NM_001199165.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0460
• Publications: 10 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.252 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP112	NM_001199165.4	MANE Select	c.471-4845A>G		intron	N/A	NP_001186094.1
	CEP112	NM_001353129.2		c.471-4845A>G		intron	N/A	NP_001340058.1
	CEP112	NM_001353127.2		c.471-4845A>G		intron	N/A	NP_001340056.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP112	ENST00000535342.7	TSL:2 MANE Select	c.471-4845A>G		intron	N/A	ENSP00000442784.2
	CEP112	ENST00000537949.5	TSL:1	c.471-4845A>G		intron	N/A	ENSP00000440775.1
	CEP112	ENST00000583358.1	TSL:1	c.471-4845A>G		intron	N/A	ENSP00000463914.1

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32107 AN: 151972 Hom.: 3721 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.211 AC: 32100 AN: 152088 Hom.: 3721 Cov.: 32 AF XY: 0.211 AC XY: 15693 AN XY: 74360

African (AFR) AF: 0.146 AC: 6059 AN: 41514

American (AMR) AF: 0.197 AC: 3006 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 1236 AN: 3468

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5180

South Asian (SAS) AF: 0.127 AC: 614 AN: 4824

European-Finnish (FIN) AF: 0.294 AC: 3094 AN: 10534

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17364 AN: 67986

Other (OTH) AF: 0.226 AC: 476 AN: 2104

Alfa AF: 0.225 Hom.: 5331

Bravo AF: 0.202

Asia WGS AF: 0.0700 AC: 247 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.9
DANN	Benign	0.69
PhyloP100		0.046
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: rs7209395; hg19: chr17-64133726;