rs2295899

chr6-159781135-G-A

Variant summary

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

The NM_030752.3(TCP1):c.798-25C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 1,536,860 control chromosomes in the GnomAD database, including 237,041 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 0.48 (19073 hom., cov: 33)
  • Exomes 𝑓: 0.56 (217968 hom.)
• Consequence: TCP1 NM_030752.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCP1	NM_030752.3	c.798-25C>T		intron_variant		ENST00000321394.12
TCP1	NM_001008897.2	c.333-25C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCP1	ENST00000321394.12	c.798-25C>T		intron_variant		1	NM_030752.3	P1

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73283 AN: 151998 Hom.: 19064 Cov.: 33

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.562

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.480

GnomAD3 exomes AF: 0.533 AC: 104567 AN: 196162 Hom.: 29244 AF XY: 0.535 AC XY: 57271 AN XY: 107068

Gnomad AFR exome AF: 0.306

Gnomad AMR exome AF: 0.652

Gnomad ASJ exome AF: 0.561

Gnomad EAS exome AF: 0.192

Gnomad SAS exome AF: 0.515

Gnomad FIN exome AF: 0.576

Gnomad NFE exome AF: 0.582

Gnomad OTH exome AF: 0.564

GnomAD4 exome AF: 0.556 AC: 769685 AN: 1384744 Hom.: 217968 Cov.: 26 AF XY: 0.554 AC XY: 379707 AN XY: 685894

Gnomad4 AFR exome AF: 0.306

Gnomad4 AMR exome AF: 0.636

Gnomad4 ASJ exome AF: 0.554

Gnomad4 EAS exome AF: 0.184

Gnomad4 SAS exome AF: 0.507

Gnomad4 FIN exome AF: 0.581

Gnomad4 NFE exome AF: 0.578

Gnomad4 OTH exome AF: 0.524

GnomAD4 genome AF: 0.482 AC: 73298 AN: 152116 Hom.: 19073 Cov.: 33 AF XY: 0.480 AC XY: 35691 AN XY: 74374

Gnomad4 AFR AF: 0.305

Gnomad4 AMR AF: 0.555

Gnomad4 ASJ AF: 0.562

Gnomad4 EAS AF: 0.183

Gnomad4 SAS AF: 0.496

Gnomad4 FIN AF: 0.571

Gnomad4 NFE AF: 0.577

Gnomad4 OTH AF: 0.475

Alfa AF: 0.530 Hom.: 4601

Bravo AF: 0.472

Asia WGS AF: 0.359 AC: 1247 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	0.53
Dann	Benign	0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2295899; hg19: chr6-160202167; COSMIC: COSV58457922; COSMIC: COSV58457922;