rs965951

Positions:

• chr21-29060236-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.1569+305C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 182,016 control chromosomes in the GnomAD database, including 2,476 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 (2251 hom., cov: 32)
  • Exomes 𝑓: 0.11 (225 hom.)
• Consequence: CCT8 NM_006585.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.617

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCT8	NM_006585.4	c.1569+305C>T		intron_variant		ENST00000286788.9	NP_006576.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCT8	ENST00000286788.9	c.1569+305C>T		intron_variant		1	NM_006585.4	ENSP00000286788	P1

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24036 AN: 151928 Hom.: 2249 Cov.: 32

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.0651

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.156

GnomAD4 exome AF: 0.108 AC: 3248 AN: 29970 Hom.: 225 AF XY: 0.105 AC XY: 1696 AN XY: 16078

Gnomad4 AFR exome AF: 0.268

Gnomad4 AMR exome AF: 0.154

Gnomad4 ASJ exome AF: 0.0983

Gnomad4 EAS exome AF: 0.0647

Gnomad4 SAS exome AF: 0.107

Gnomad4 FIN exome AF: 0.0572

Gnomad4 NFE exome AF: 0.105

Gnomad4 OTH exome AF: 0.115

GnomAD4 genome AF: 0.158 AC: 24058 AN: 152046 Hom.: 2251 Cov.: 32 AF XY: 0.154 AC XY: 11469 AN XY: 74316

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.145

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.0651

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.157

Alfa AF: 0.144 Hom.: 231

Bravo AF: 0.170

Asia WGS AF: 0.148 AC: 518 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.7
DANN	Benign	0.27

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: rs965951; hg19: chr21-30432557;