dbSNP rs2295899: TCP1:c.798-25C>T (chr6-159781135-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.07

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
TCP1	NM_030752.3 link	c.798-25C>T		intron_variant	Intron 7 of 11	ENST00000321394.12	NP_110379.2	P17987
TCP1	NM_001008897.2 link	c.333-25C>T		intron_variant	Intron 6 of 10		NP_001008897.1	E7EQR6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCP1	ENST00000321394.12 link	c.798-25C>T		intron_variant	Intron 7 of 11	1	NM_030752.3	ENSP00000317334.7		P17987

Frequencies

GnomAD3 genomes

AF:

0.482

AC:

73283

AN:

151998

Hom.:

19064

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.554

AC XY:

379707

AN XY:

685894

show subpopulations

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.:

AF XY:

0.480

AC XY:

35691

AN XY:

74374

show subpopulations

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over