chr8-67064144-C-G

Position:

• chr8-67064144-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000518747.1(COPS5):​c.-93G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0744 in 520,886 control chromosomes in the GnomAD database, including 3,490 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (2457 hom., cov: 31)
  • Exomes 𝑓: 0.053 (1033 hom.)
• Consequence: COPS5 ENST00000518747.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.109

Genes affected

COPS5 (HGNC:2240): (COP9 signalosome subunit 5) The protein encoded by this gene is one of the eight subunits of COP9 signalosome, a highly conserved protein complex that functions as an important regulator in multiple signaling pathways. The structure and function of COP9 signalosome is similar to that of the 19S regulatory particle of 26S proteasome. COP9 signalosome has been shown to interact with SCF-type E3 ubiquitin ligases and act as a positive regulator of E3 ubiquitin ligases. This protein is reported to be involved in the degradation of cyclin-dependent kinase inhibitor CDKN1B/p27Kip1. It is also known to be an coactivator that increases the specificity of JUN/AP1 transcription factors. [provided by RefSeq, Jul 2008]

CSPP1 (HGNC:26193): (centrosome and spindle pole associated protein 1) This gene encodes a centrosome and spindle pole associated protein. The encoded protein plays a role in cell-cycle progression and spindle organization, regulates cytokinesis, interacts with Nephrocystin 8 and is required for cilia formation. Mutations in this gene result in primary cilia abnormalities and classical Joubert syndrome. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Apr 2014]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 8-67064144-C-G is Benign according to our data. Variant chr8-67064144-C-G is described in ClinVar as [Benign]. Clinvar id is 1259932.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COPS5	ENST00000518747.1	c.-93G>C		5_prime_UTR_variant	1/5	3
COPS5	ENST00000517736.5	c.-50+287G>C		intron_variant		5
CSPP1	ENST00000676113.1	c.-11+1624C>G		intron_variant				P4

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19311 AN: 151906 Hom.: 2446 Cov.: 31

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0891

Gnomad ASJ AF: 0.0481

Gnomad EAS AF: 0.0255

Gnomad SAS AF: 0.0867

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0321

Gnomad OTH AF: 0.105

GnomAD4 exome AF: 0.0526 AC: 19407 AN: 368862 Hom.: 1033 Cov.: 0 AF XY: 0.0527 AC XY: 10309 AN XY: 195544

Gnomad4 AFR exome AF: 0.311

Gnomad4 AMR exome AF: 0.0844

Gnomad4 ASJ exome AF: 0.0415

Gnomad4 EAS exome AF: 0.0339

Gnomad4 SAS exome AF: 0.0768

Gnomad4 FIN exome AF: 0.102

Gnomad4 NFE exome AF: 0.0317

Gnomad4 OTH exome AF: 0.0628

GnomAD4 genome AF: 0.127 AC: 19367 AN: 152024 Hom.: 2457 Cov.: 31 AF XY: 0.130 AC XY: 9642 AN XY: 74348

Gnomad4 AFR AF: 0.326

Gnomad4 AMR AF: 0.0892

Gnomad4 ASJ AF: 0.0481

Gnomad4 EAS AF: 0.0255

Gnomad4 SAS AF: 0.0860

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.0321

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0904 Hom.: 180

Bravo AF: 0.133

Asia WGS AF: 0.0760 AC: 262 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.9
DANN	Benign	0.51

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs73691193; hg19: chr8-67976379;