dbSNP rs2295898: TCP1:c.798-140G>C (chr6-159781250-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.262

Publications

8 publications found

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 Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics
intellectual developmental disorder with polymicrogyria and seizures
Inheritance: AD Classification: MODERATE Submitted by: G2P

TCP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TCP1	NM_030752.3 link	c.798-140G>C		intron_variant	Intron 7 of 11	ENST00000321394.12	NP_110379.2	P17987
TCP1	NM_001008897.2 link	c.333-140G>C		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.798-140G>C		intron_variant	Intron 7 of 11	1	NM_030752.3	ENSP00000317334.7		P17987

Frequencies

GnomAD3 genomes

AF:

0.139

AC:

21132

AN:

152020

Hom.:

1818

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.0550

AC:

724

AN:

13172

American (AMR)

AF:

0.160

AC:

1753

AN:

10974

Ashkenazi Jewish (ASJ)

AF:

0.0952

AC:

1260

AN:

13232

East Asian (EAS)

AF:

0.370

AC:

9557

AN:

25798

South Asian (SAS)

AF:

0.200

AC:

6133

AN:

30662

European-Finnish (FIN)

AF:

0.204

AC:

6030

AN:

29524

Middle Eastern (MID)

AF:

0.167

AC:

402

AN:

2406

European-Non Finnish (NFE)

AF:

0.135

AC:

63976

AN:

473868

Other (OTH)

AF:

0.150

AC:

4527

AN:

30224

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

3743

7486

11228

14971

18714

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1860

3720

5580

7440

9300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.139

AC:

21132

AN:

152140

Hom.:

1818

Cov.:

AF XY:

0.146

AC XY:

10886

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.0659

AC:

2733

AN:

41500

American (AMR)

AF:

0.165

AC:

2527

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0928

AC:

322

AN:

3470

East Asian (EAS)

AF:

0.397

AC:

2054

AN:

5174

South Asian (SAS)

AF:

0.231

AC:

1115

AN:

4828

European-Finnish (FIN)

AF:

0.224

AC:

2366

AN:

10564

Middle Eastern (MID)

AF:

0.116

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.142

AC:

9629

AN:

67992

Other (OTH)

AF:

0.158

AC:

333

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

924

1847

2771

3694

4618

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

240

480

720

960

1200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.78

PhyloP100

-0.26

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over