rs2070611

chr21-29073453-G-C

Variant summary

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

The NM_006585.4(CCT8):c.60+78C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 1,607,270 control chromosomes in the GnomAD database, including 13,724 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 (2209 hom., cov: 33)
  • Exomes 𝑓: 0.12 (11515 hom.)
• Consequence: CCT8 NM_006585.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.607

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCT8	NM_006585.4	c.60+78C>G		intron_variant		ENST00000286788.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCT8	ENST00000286788.9	c.60+78C>G		intron_variant		1	NM_006585.4	P1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23953 AN: 152102 Hom.: 2208 Cov.: 33

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.0429

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.0652

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.157

GnomAD4 exome AF: 0.121 AC: 176551 AN: 1455048 Hom.: 11515 Cov.: 33 AF XY: 0.120 AC XY: 86735 AN XY: 723352

Gnomad4 AFR exome AF: 0.270

Gnomad4 AMR exome AF: 0.176

Gnomad4 ASJ exome AF: 0.131

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: 0.139

GnomAD4 genome AF: 0.157 AC: 23973 AN: 152222 Hom.: 2209 Cov.: 33 AF XY: 0.153 AC XY: 11418 AN XY: 74446

Gnomad4 AFR AF: 0.258

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.146

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.0652

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.158

Alfa AF: 0.144 Hom.: 231

Bravo AF: 0.169

Asia WGS AF: 0.149 AC: 520 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	5.6
Dann	Benign	0.54

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: rs2070611; hg19: chr21-30445774; COSMIC: COSV54505828; COSMIC: COSV54505828;