chr12-69601493-T-C

Position:

• chr12-69601493-T-C

Variant summary

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

The ENST00000299300.11(CCT2):​c.*168T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 1,475,088 control chromosomes in the GnomAD database, including 31,165 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 0.18 (2793 hom., cov: 32)
  • Exomes 𝑓: 0.20 (28372 hom.)
• Consequence: CCT2 ENST00000299300.11 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.18

Genes affected

CCT2 (HGNC:1615): (chaperonin containing TCP1 subunit 2) The protein encoded by this gene is a molecular chaperone that is a member of the chaperonin containing TCP1 complex (CCT), also known as the TCP1 ring complex (TRiC). This complex consists of two identical stacked rings, each containing eight different proteins. Unfolded polypeptides enter the central cavity of the complex and are folded in an ATP-dependent manner. The complex folds various proteins, including actin and tubulin. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCT2	NM_006431.3	c.*168T>C		3_prime_UTR_variant	16/16	ENST00000299300.11	NP_006422.1
CCT2	NM_001198842.2	c.*168T>C		3_prime_UTR_variant	16/16		NP_001185771.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCT2	ENST00000299300.11	c.*168T>C		3_prime_UTR_variant	16/16	1	NM_006431.3	ENSP00000299300	P1

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27753 AN: 152098 Hom.: 2789 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.198

GnomAD3 exomes AF: 0.214 AC: 23023 AN: 107456 Hom.: 2603 AF XY: 0.219 AC XY: 12582 AN XY: 57366

Gnomad AFR exome AF: 0.104

Gnomad AMR exome AF: 0.172

Gnomad ASJ exome AF: 0.248

Gnomad EAS exome AF: 0.279

Gnomad SAS exome AF: 0.264

Gnomad FIN exome AF: 0.210

Gnomad NFE exome AF: 0.213

Gnomad OTH exome AF: 0.236

GnomAD4 exome AF: 0.204 AC: 269481 AN: 1322874 Hom.: 28372 Cov.: 26 AF XY: 0.206 AC XY: 133556 AN XY: 648566

Gnomad4 AFR exome AF: 0.109

Gnomad4 AMR exome AF: 0.175

Gnomad4 ASJ exome AF: 0.236

Gnomad4 EAS exome AF: 0.220

Gnomad4 SAS exome AF: 0.256

Gnomad4 FIN exome AF: 0.198

Gnomad4 NFE exome AF: 0.202

Gnomad4 OTH exome AF: 0.209

GnomAD4 genome AF: 0.182 AC: 27771 AN: 152214 Hom.: 2793 Cov.: 32 AF XY: 0.185 AC XY: 13772 AN XY: 74420

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.239

Gnomad4 EAS AF: 0.271

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.212

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.199

Alfa AF: 0.209 Hom.: 6139

Bravo AF: 0.177

Asia WGS AF: 0.272 AC: 946 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	12
DANN	Benign	0.72

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: rs7200; hg19: chr12-69995273; COSMIC: COSV54739361; COSMIC: COSV54739361;