rs2070610

Positions:

• chr21-29073627-G-A

Variant summary

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

The NM_006585.4(CCT8):​c.-37C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,602,780 control chromosomes in the GnomAD database, including 14,324 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 0.16 (2485 hom., cov: 34)
  • Exomes 𝑓: 0.12 (11839 hom.)
• Consequence: CCT8 NM_006585.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.337

Genes affected

CCT8 (HGNC:1623): (chaperonin containing TCP1 subunit 8) This gene encodes the theta subunit of the CCT chaperonin, which is abundant in the eukaryotic cytosol and may be involved in the transport and assembly of newly synthesized proteins. Alternative splicing results in multiple transcript variants of this gene. A pseudogene related to this gene is located on chromosome 1. [provided by RefSeq, Sep 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCT8	NM_006585.4	c.-37C>T		5_prime_UTR_variant	1/15	ENST00000286788.9	NP_006576.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCT8	ENST00000286788.9	c.-37C>T		5_prime_UTR_variant	1/15	1	NM_006585.4	ENSP00000286788	P1
CCT8	ENST00000470450.5	n.13C>T		non_coding_transcript_exon_variant	1/15	1
CCT8	ENST00000540844.5	c.-176C>T		5_prime_UTR_variant	1/14	2		ENSP00000442730
CCT8	ENST00000484403.5			upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25074 AN: 152102 Hom.: 2479 Cov.: 34

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.0651

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.168

GnomAD3 exomes AF: 0.137 AC: 34246 AN: 250334 Hom.: 2677 AF XY: 0.131 AC XY: 17705 AN XY: 135460

Gnomad AFR exome AF: 0.287

Gnomad AMR exome AF: 0.180

Gnomad ASJ exome AF: 0.141

Gnomad EAS exome AF: 0.160

Gnomad SAS exome AF: 0.112

Gnomad FIN exome AF: 0.0673

Gnomad NFE exome AF: 0.118

Gnomad OTH exome AF: 0.128

GnomAD4 exome AF: 0.122 AC: 177442 AN: 1450558 Hom.: 11839 Cov.: 27 AF XY: 0.121 AC XY: 87196 AN XY: 722264

Gnomad4 AFR exome AF: 0.297

Gnomad4 AMR exome AF: 0.177

Gnomad4 ASJ exome AF: 0.139

Gnomad4 EAS exome AF: 0.103

Gnomad4 SAS exome AF: 0.112

Gnomad4 FIN exome AF: 0.0704

Gnomad4 NFE exome AF: 0.117

Gnomad4 OTH exome AF: 0.142

GnomAD4 genome AF: 0.165 AC: 25104 AN: 152222 Hom.: 2485 Cov.: 34 AF XY: 0.160 AC XY: 11932 AN XY: 74446

Gnomad4 AFR AF: 0.283

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.0651

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.168

Alfa AF: 0.132 Hom.: 1528

Bravo AF: 0.177

Asia WGS AF: 0.152 AC: 529 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.7
DANN	Benign	0.83

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: rs2070610; hg19: chr21-30445948; COSMIC: COSV54504600; COSMIC: COSV54504600;