rs1547093

Positions:

• chr6-159784959-C-A

Variant summary

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

The ENST00000321394.12(TCP1):​c.489-112G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.79 in 1,030,764 control chromosomes in the GnomAD database, including 323,952 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 0.78 (46361 hom., cov: 32)
  • Exomes 𝑓: 0.79 (277591 hom.)
• Consequence: TCP1 ENST00000321394.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0570

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCP1	NM_030752.3	c.489-112G>T		intron_variant		ENST00000321394.12	NP_110379.2
TCP1	NM_001008897.2	c.24-112G>T		intron_variant			NP_001008897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCP1	ENST00000321394.12	c.489-112G>T		intron_variant		1	NM_030752.3	ENSP00000317334	P1

Frequencies

GnomAD3 genomes AF: 0.778 AC: 118330 AN: 152056 Hom.: 46333 Cov.: 32

Gnomad AFR AF: 0.738

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.837

Gnomad ASJ AF: 0.747

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.852

Gnomad FIN AF: 0.843

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.792

Gnomad OTH AF: 0.792

GnomAD4 exome AF: 0.792 AC: 696204 AN: 878588 Hom.: 277591 Cov.: 11 AF XY: 0.795 AC XY: 364706 AN XY: 458990

Gnomad4 AFR exome AF: 0.729

Gnomad4 AMR exome AF: 0.862

Gnomad4 ASJ exome AF: 0.739

Gnomad4 EAS exome AF: 0.563

Gnomad4 SAS exome AF: 0.848

Gnomad4 FIN exome AF: 0.842

Gnomad4 NFE exome AF: 0.796

Gnomad4 OTH exome AF: 0.781

GnomAD4 genome AF: 0.778 AC: 118410 AN: 152176 Hom.: 46361 Cov.: 32 AF XY: 0.781 AC XY: 58141 AN XY: 74406

Gnomad4 AFR AF: 0.738

Gnomad4 AMR AF: 0.837

Gnomad4 ASJ AF: 0.747

Gnomad4 EAS AF: 0.587

Gnomad4 SAS AF: 0.851

Gnomad4 FIN AF: 0.843

Gnomad4 NFE AF: 0.792

Gnomad4 OTH AF: 0.784

Alfa AF: 0.784 Hom.: 11667

Bravo AF: 0.773

Asia WGS AF: 0.705 AC: 2451 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.4
DANN	Benign	0.41

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: rs1547093; hg19: chr6-160205991;