ENST00000262210:c.-56G>A

Variant names:

• chr8-67064343-G-A
• rs367781331
• ENST00000262210.11:c.-56G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000262210.11(CSPP1):​c.-56G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00124 in 1,581,962 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0015 (4 hom., cov: 31)
  • Exomes 𝑓: 0.0012 (25 hom.)
• Consequence: CSPP1 ENST00000262210.11 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.30
• Publications: 1 publications found

Genes affected

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]

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]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 8-67064343-G-A is Benign according to our data. Variant chr8-67064343-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1205527.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00151 (230/152262) while in subpopulation EAS AF = 0.0144 (74/5154). AF 95% confidence interval is 0.0117. There are 4 homozygotes in GnomAd4. There are 149 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000262210.11. 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
	CSPP1	NM_001382391.1	MANE Select	c.-206G>A		upstream_gene	N/A	NP_001369320.1	A0A7I2V5W3
	CSPP1	NM_001364869.1		c.-56G>A		upstream_gene	N/A	NP_001351798.1	A0A7I2PHE7
	CSPP1	NM_024790.7		c.-56G>A		upstream_gene	N/A	NP_079066.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSPP1	ENST00000262210.11	TSL:1	c.-56G>A		5_prime_UTR	Exon 1 of 30	ENSP00000262210.6	A0A7I2PHE7
	CSPP1	ENST00000675306.2		c.-206G>A		5_prime_UTR	Exon 1 of 28	ENSP00000502421.1	A0A6Q8PGS3
	CSPP1	ENST00000678017.1		c.-729G>A		5_prime_UTR	Exon 1 of 25	ENSP00000504394.1	A0A7I2V5P5

Frequencies

GnomAD3 genomes AF: 0.00152 AC: 231 AN: 152144 Hom.: 4 Cov.: 31

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.0143

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00951

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000588

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.00121 AC: 1727 AN: 1429700 Hom.: 25 Cov.: 30 AF XY: 0.00125 AC XY: 884 AN XY: 709724

African (AFR) AF: 0.00 AC: 0 AN: 33104

American (AMR) AF: 0.00 AC: 0 AN: 40390

Ashkenazi Jewish (ASJ) AF: 0.00249 AC: 63 AN: 25256

East Asian (EAS) AF: 0.0165 AC: 644 AN: 39072

South Asian (SAS) AF: 0.00115 AC: 96 AN: 83436

European-Finnish (FIN) AF: 0.0107 AC: 493 AN: 46002

Middle Eastern (MID) AF: 0.00104 AC: 5 AN: 4812

European-Non Finnish (NFE) AF: 0.000290 AC: 319 AN: 1098446

Other (OTH) AF: 0.00181 AC: 107 AN: 59182

GnomAD4 genome AF: 0.00151 AC: 230 AN: 152262 Hom.: 4 Cov.: 31 AF XY: 0.00200 AC XY: 149 AN XY: 74450

African (AFR) AF: 0.0000241 AC: 1 AN: 41564

American (AMR) AF: 0.00 AC: 0 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3466

East Asian (EAS) AF: 0.0144 AC: 74 AN: 5154

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4828

European-Finnish (FIN) AF: 0.00951 AC: 101 AN: 10622

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

European-Non Finnish (NFE) AF: 0.000588 AC: 40 AN: 68014

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.00111 Hom.: 0

Bravo AF: 0.00115

Asia WGS AF: 0.0120 AC: 40 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely 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	-0.81
CADD	Benign	0.48
DANN	Benign	0.83
PhyloP100		-1.3
PromoterAI		-0.10	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs367781331; hg19: chr8-67976578; COSMIC: COSV51586746; COSMIC: COSV51586746;