dbSNP rs3818298: TCP1:c.378-188A>G (chr6-159785684-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_030752.3(TCP1):c.378-188A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 791,580 control chromosomes in the GnomAD database, including 17,942 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 0.20 ( 3170 hom., cov: 33)

Exomes 𝑓: 0.21 ( 14772 hom. )

Consequence

TCP1
NM_030752.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.80

Publications

15 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 links:

SNORA29 (HGNC:32619): (small nucleolar RNA, H/ACA box 29)

SNORA29 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.25).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TCP1	NM_030752.3 link	c.378-188A>G	intron_variant	Intron 4 of 11	ENST00000321394.12	NP_110379.2	P17987
SNORA29	NR_002965.1 link	n.50A>G	non_coding_transcript_exon_variant	Exon 1 of 1
TCP1	NM_001008897.2 link	c.-88-188A>G	intron_variant	Intron 3 of 10		NP_001008897.1	E7EQR6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCP1	ENST00000321394.12 link	c.378-188A>G		intron_variant	Intron 4 of 11	1	NM_030752.3	ENSP00000317334.7		P17987

Frequencies

GnomAD3 genomes

AF:

0.199

AC:

30206

AN:

151978

Hom.:

3169

Cov.:

show subpopulations

Gnomad AFR

AF:

0.181

Gnomad AMI

AF:

0.124

Gnomad AMR

AF:

0.205

Gnomad ASJ

AF:

0.118

Gnomad EAS

AF:

0.403

Gnomad SAS

AF:

0.280

Gnomad FIN

AF:

0.253

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.183

Gnomad OTH

AF:

0.210

GnomAD2 exomes

AF:

0.210

AC:

49131

AN:

233618

AF XY:

0.214

show subpopulations

Gnomad AFR exome

AF:

0.177

Gnomad AMR exome

AF:

0.174

Gnomad ASJ exome

AF:

0.121

Gnomad EAS exome

AF:

0.394

Gnomad FIN exome

AF:

0.247

Gnomad NFE exome

AF:

0.185

Gnomad OTH exome

AF:

0.200

GnomAD4 exome

AF:

0.207

AC:

132349

AN:

639484

Hom.:

14772

Cov.:

AF XY:

0.210

AC XY:

73104

AN XY:

347824

show subpopulations

African (AFR)

AF:

0.176

AC:

3185

AN:

18090

American (AMR)

AF:

0.179

AC:

7762

AN:

43482

Ashkenazi Jewish (ASJ)

AF:

0.125

AC:

2633

AN:

21082

East Asian (EAS)

AF:

0.380

AC:

13708

AN:

36110

South Asian (SAS)

AF:

0.267

AC:

18394

AN:

68890

European-Finnish (FIN)

AF:

0.241

AC:

9189

AN:

38164

Middle Eastern (MID)

AF:

0.208

AC:

873

AN:

4188

European-Non Finnish (NFE)

AF:

0.186

AC:

69900

AN:

375596

Other (OTH)

AF:

0.198

AC:

6705

AN:

33882

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

5285

10569

15854

21138

26423

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

790

1580

2370

3160

3950

<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:

0.199

AC:

30217

AN:

152096

Hom.:

3170

Cov.:

AF XY:

0.205

AC XY:

15235

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.181

AC:

7525

AN:

41504

American (AMR)

AF:

0.204

AC:

3120

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.118

AC:

409

AN:

3470

East Asian (EAS)

AF:

0.403

AC:

2084

AN:

5176

South Asian (SAS)

AF:

0.281

AC:

1354

AN:

4824

European-Finnish (FIN)

AF:

0.253

AC:

2668

AN:

10548

Middle Eastern (MID)

AF:

0.156

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.183

AC:

12455

AN:

67978

Other (OTH)

AF:

0.210

AC:

443

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1231

2462

3692

4923

6154

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

324

648

972

1296

1620

<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:

0.183

Hom.:

1437

Bravo

AF:

0.192

Asia WGS

AF:

0.300

AC:

1040

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Benign

0.91

PhyloP100

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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