rs2295898

Positions:

• chr6-159781250-C-G

Variant summary

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

The NM_030752.3(TCP1):​c.798-140G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 782,000 control chromosomes in the GnomAD database, including 10,242 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 0.14 (1818 hom., cov: 33)
  • Exomes 𝑓: 0.15 (8424 hom.)
• Consequence: TCP1 NM_030752.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.262

Genes affected

TCP1 (HGNC:11655): (t-complex 1) 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. Alternate transcriptional splice variants of this gene, encoding different isoforms, have been characterized. In addition, three pseudogenes that appear to be derived from this gene have been found. [provided by RefSeq, Jun 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCP1	NM_030752.3	c.798-140G>C		intron_variant		ENST00000321394.12
TCP1	NM_001008897.2	c.333-140G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCP1	ENST00000321394.12	c.798-140G>C		intron_variant		1	NM_030752.3	P1

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21132 AN: 152020 Hom.: 1818 Cov.: 33

Gnomad AFR AF: 0.0660

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.0928

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.158

GnomAD4 exome AF: 0.150 AC: 94362 AN: 629860 Hom.: 8424 AF XY: 0.151 AC XY: 47977 AN XY: 317090

Gnomad4 AFR exome AF: 0.0550

Gnomad4 AMR exome AF: 0.160

Gnomad4 ASJ exome AF: 0.0952

Gnomad4 EAS exome AF: 0.370

Gnomad4 SAS exome AF: 0.200

Gnomad4 FIN exome AF: 0.204

Gnomad4 NFE exome AF: 0.135

Gnomad4 OTH exome AF: 0.150

GnomAD4 genome AF: 0.139 AC: 21132 AN: 152140 Hom.: 1818 Cov.: 33 AF XY: 0.146 AC XY: 10886 AN XY: 74374

Gnomad4 AFR AF: 0.0659

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.0928

Gnomad4 EAS AF: 0.397

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.158

Alfa AF: 0.136 Hom.: 189

Bravo AF: 0.131

Asia WGS AF: 0.271 AC: 939 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.8
DANN	Benign	0.78

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: rs2295898; hg19: chr6-160202282; COSMIC: COSV58458956; COSMIC: COSV58458956;