rs4761246

Positions:

• chr12-69598668-G-A

Variant summary

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

The NM_006431.3(CCT2):​c.1435+247G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,136 control chromosomes in the GnomAD database, including 2,790 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 (2790 hom., cov: 33)
• Consequence: CCT2 NM_006431.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.708

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=-0.86).
• 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.1435+247G>A		intron_variant		ENST00000299300.11	NP_006422.1
CCT2	NM_001198842.2	c.1294+247G>A		intron_variant			NP_001185771.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCT2	ENST00000299300.11	c.1435+247G>A		intron_variant		1	NM_006431.3	ENSP00000299300	P1
CCT2	ENST00000543146.2	c.1294+247G>A		intron_variant		2		ENSP00000445471
CCT2	ENST00000544368.6	c.1435+247G>A		intron_variant		5		ENSP00000441847
CCT2	ENST00000550010.5	c.*80+247G>A		intron_variant, NMD_transcript_variant		5		ENSP00000450153

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27725 AN: 152018 Hom.: 2786 Cov.: 33

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.270

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

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.182 AC: 27743 AN: 152136 Hom.: 2790 Cov.: 33 AF XY: 0.185 AC XY: 13752 AN XY: 74372

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.239

Gnomad4 EAS AF: 0.271

Gnomad4 SAS AF: 0.245

Gnomad4 FIN AF: 0.212

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.199

Alfa AF: 0.180 Hom.: 340

Bravo AF: 0.177

Asia WGS AF: 0.271 AC: 943 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.9
DANN	Benign	0.66

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: rs4761246; hg19: chr12-69992448;