rs1547094

Positions:

• chr6-159785083-A-C

Variant summary

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

The NM_030752.3(TCP1):​c.489-236T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 609,758 control chromosomes in the GnomAD database, including 14,924 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 0.22 (3811 hom., cov: 33)
  • Exomes 𝑓: 0.21 (11113 hom.)
• Consequence: TCP1 NM_030752.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.812

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]

TCP1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCP1	NM_030752.3	c.489-236T>G		intron_variant		ENST00000321394.12	NP_110379.2
TCP1	NM_001008897.2	c.24-236T>G		intron_variant			NP_001008897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCP1	ENST00000321394.12	c.489-236T>G		intron_variant		1	NM_030752.3	ENSP00000317334.7

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33294 AN: 152066 Hom.: 3808 Cov.: 33

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.227

GnomAD4 exome AF: 0.212 AC: 96814 AN: 457576 Hom.: 11113 Cov.: 4 AF XY: 0.214 AC XY: 52091 AN XY: 243098

Gnomad4 AFR exome AF: 0.241

Gnomad4 AMR exome AF: 0.195

Gnomad4 ASJ exome AF: 0.126

Gnomad4 EAS exome AF: 0.378

Gnomad4 SAS exome AF: 0.269

Gnomad4 FIN exome AF: 0.240

Gnomad4 NFE exome AF: 0.185

Gnomad4 OTH exome AF: 0.206

GnomAD4 genome AF: 0.219 AC: 33318 AN: 152182 Hom.: 3811 Cov.: 33 AF XY: 0.225 AC XY: 16757 AN XY: 74394

Gnomad4 AFR AF: 0.252

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.402

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.251

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.226

Alfa AF: 0.197 Hom.: 383

Bravo AF: 0.216

Asia WGS AF: 0.305 AC: 1058 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.6
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1547094; hg19: chr6-160206115;