12-69597895-T-C

Variant names:

• chr12-69597895-T-C
• rs35639
• NM_006431.3:c.1232-73T>C

Variant summary

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

The NM_006431.3(CCT2):​c.1232-73T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0359 in 1,451,628 control chromosomes in the GnomAD database, including 4,669 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 0.051 (553 hom., cov: 33)
  • Exomes 𝑓: 0.034 (4116 hom.)
• Consequence: CCT2 NM_006431.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.129

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCT2	NM_006431.3	c.1232-73T>C		intron_variant	Intron 12 of 15	ENST00000299300.11	NP_006422.1
CCT2	NM_001198842.2	c.1091-73T>C		intron_variant	Intron 12 of 15		NP_001185771.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCT2	ENST00000299300.11	c.1232-73T>C		intron_variant	Intron 12 of 15	1	NM_006431.3	ENSP00000299300.6
CCT2	ENST00000544368.6	c.1232-73T>C		intron_variant	Intron 12 of 14	5		ENSP00000441847.2
CCT2	ENST00000543146.2	c.1091-73T>C		intron_variant	Intron 12 of 15	2		ENSP00000445471.2
CCT2	ENST00000550010.5	n.1231+129T>C		intron_variant	Intron 12 of 14	5		ENSP00000450153.1

Frequencies

GnomAD3 genomes AF: 0.0512 AC: 7793 AN: 152206 Hom.: 552 Cov.: 33

Gnomad AFR AF: 0.0746

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0649

Gnomad ASJ AF: 0.0132

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.0542

Gnomad FIN AF: 0.0172

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0168

Gnomad OTH AF: 0.0487

GnomAD4 exome AF: 0.0341 AC: 44257 AN: 1299304 Hom.: 4116 Cov.: 18 AF XY: 0.0338 AC XY: 21978 AN XY: 649688

Gnomad4 AFR exome AF: 0.0729

Gnomad4 AMR exome AF: 0.103

Gnomad4 ASJ exome AF: 0.0138

Gnomad4 EAS exome AF: 0.418

Gnomad4 SAS exome AF: 0.0487

Gnomad4 FIN exome AF: 0.0199

Gnomad4 NFE exome AF: 0.0153

Gnomad4 OTH exome AF: 0.0447

GnomAD4 genome AF: 0.0512 AC: 7797 AN: 152324 Hom.: 553 Cov.: 33 AF XY: 0.0524 AC XY: 3903 AN XY: 74494

Gnomad4 AFR AF: 0.0746

Gnomad4 AMR AF: 0.0647

Gnomad4 ASJ AF: 0.0132

Gnomad4 EAS AF: 0.373

Gnomad4 SAS AF: 0.0538

Gnomad4 FIN AF: 0.0172

Gnomad4 NFE AF: 0.0168

Gnomad4 OTH AF: 0.0473

Alfa AF: 0.0244 Hom.: 27

Bravo AF: 0.0599

Asia WGS AF: 0.163 AC: 565 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.9
DANN	Benign	0.74

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: rs35639; hg19: chr12-69991675;