chr17-65637177-C-A

Variant names:

• chr17-65637177-C-A
• rs75033823
• NM_001199165.4:c.2811G>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001199165.4(CEP112):​c.2811G>T​(p.Leu937Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00214 in 1,613,708 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0094 (20 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (32 hom.)
• Consequence: CEP112 NM_001199165.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.113
• Publications: 1 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)

ENSG00000266076 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BP6: Variant 17-65637177-C-A is Benign according to our data. Variant chr17-65637177-C-A is described in ClinVar as Benign. ClinVar VariationId is 781327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.113 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00939 (1430/152266) while in subpopulation AFR AF = 0.0312 (1296/41558). AF 95% confidence interval is 0.0298. There are 20 homozygotes in GnomAd4. There are 693 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 20 Unknown gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP112	NM_001199165.4	MANE Select	c.2811G>T	p.Leu937Leu	synonymous	Exon 26 of 27	NP_001186094.1	Q8N8E3-1
	CEP112	NM_001353129.2		c.2814G>T	p.Leu938Leu	synonymous	Exon 26 of 27	NP_001340058.1
	CEP112	NM_001353127.2		c.2811G>T	p.Leu937Leu	synonymous	Exon 26 of 27	NP_001340056.1	Q8N8E3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP112	ENST00000535342.7	TSL:2 MANE Select	c.2811G>T	p.Leu937Leu	synonymous	Exon 26 of 27	ENSP00000442784.2	Q8N8E3-1
	CEP112	ENST00000537949.5	TSL:1	c.2685G>T	p.Leu895Leu	synonymous	Exon 24 of 25	ENSP00000440775.1	F5GYE8
	CEP112	ENST00000317442.12	TSL:1	c.579G>T	p.Leu193Leu	synonymous	Exon 6 of 7	ENSP00000320592.5	Q8N8E3-2

Frequencies

GnomAD3 genomes AF: 0.00940 AC: 1430 AN: 152148 Hom.: 19 Cov.: 32

Gnomad AFR AF: 0.0313

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00439

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.0110

GnomAD2 exomes AF: 0.00333 AC: 836 AN: 251146 AF XY: 0.00270

Gnomad AFR exome AF: 0.0333

Gnomad AMR exome AF: 0.00367

Gnomad ASJ exome AF: 0.00258

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000396

Gnomad OTH exome AF: 0.00539

GnomAD4 exome AF: 0.00138 AC: 2016 AN: 1461442 Hom.: 32 Cov.: 30 AF XY: 0.00133 AC XY: 968 AN XY: 727050

African (AFR) AF: 0.0301 AC: 1006 AN: 33462

American (AMR) AF: 0.00436 AC: 195 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00222 AC: 58 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.00220 AC: 190 AN: 86244

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53416

Middle Eastern (MID) AF: 0.00625 AC: 36 AN: 5764

European-Non Finnish (NFE) AF: 0.000304 AC: 338 AN: 1111642

Other (OTH) AF: 0.00318 AC: 192 AN: 60384

GnomAD4 genome AF: 0.00939 AC: 1430 AN: 152266 Hom.: 20 Cov.: 32 AF XY: 0.00931 AC XY: 693 AN XY: 74438

African (AFR) AF: 0.0312 AC: 1296 AN: 41558

American (AMR) AF: 0.00438 AC: 67 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.00228 AC: 11 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000426 AC: 29 AN: 68018

Other (OTH) AF: 0.0109 AC: 23 AN: 2116

Alfa AF: 0.00352 Hom.: 6

Bravo AF: 0.0115

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.000654

EpiControl AF: 0.000415

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	3.7
DANN	Benign	0.74
PhyloP100		0.11
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs75033823; hg19: chr17-63633295;