rs4761246

Variant names:

• chr12-69598668-G-A
• rs4761246
• NM_006431.3:c.1435+247G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

CCT2 Gene-Disease associations (from GenCC):

• Leber congenital amaurosis

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Franklin by Genoox, G2P

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CCT2	NM_006431.3	c.1435+247G>A		intron_variant	Intron 14 of 15	ENST00000299300.11	NP_006422.1
CCT2	NM_001198842.2	c.1294+247G>A		intron_variant	Intron 14 of 15		NP_001185771.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCT2	ENST00000299300.11	c.1435+247G>A		intron_variant	Intron 14 of 15	1	NM_006431.3	ENSP00000299300.6
CCT2	ENST00000544368.6	c.1435+247G>A		intron_variant	Intron 14 of 14	5		ENSP00000441847.2
CCT2	ENST00000543146.2	c.1294+247G>A		intron_variant	Intron 14 of 15	2		ENSP00000445471.2
CCT2	ENST00000550010.5	n.*80+247G>A		intron_variant	Intron 13 of 14	5		ENSP00000450153.1

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

African (AFR) AF: 0.104 AC: 4322 AN: 41504

American (AMR) AF: 0.187 AC: 2861 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 829 AN: 3472

East Asian (EAS) AF: 0.271 AC: 1403 AN: 5180

South Asian (SAS) AF: 0.245 AC: 1183 AN: 4824

European-Finnish (FIN) AF: 0.212 AC: 2241 AN: 10570

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14214 AN: 67990

Other (OTH) AF: 0.199 AC: 420 AN: 2112

Alfa AF: 0.177 Hom.: 345

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
PhyloP100		0.71
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4761246; hg19: chr12-69992448;