dbSNP rs1547094: TCP1:c.489-236T>G (chr6-159785083-A-C) – 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.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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.812

Publications

4 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=-0.84).

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 rank	MANE	Protein	UniProt
TCP1	NM_030752.3 link	c.489-236T>G		intron_variant	Intron 5 of 11	ENST00000321394.12	NP_110379.2	P17987
TCP1	NM_001008897.2 link	c.24-236T>G		intron_variant	Intron 4 of 10		NP_001008897.1	E7EQR6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCP1	ENST00000321394.12 link	c.489-236T>G		intron_variant	Intron 5 of 11	1	NM_030752.3	ENSP00000317334.7		P17987

Frequencies

GnomAD3 genomes

AF:

0.219

AC:

33294

AN:

152066

Hom.:

3808

Cov.:

show subpopulations

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.:

AF XY:

0.214

AC XY:

52091

AN XY:

243098

show subpopulations

African (AFR)

AF:

0.241

AC:

3030

AN:

12588

American (AMR)

AF:

0.195

AC:

3459

AN:

17776

Ashkenazi Jewish (ASJ)

AF:

0.126

AC:

1759

AN:

13930

East Asian (EAS)

AF:

0.378

AC:

11736

AN:

31032

South Asian (SAS)

AF:

0.269

AC:

12104

AN:

44976

European-Finnish (FIN)

AF:

0.240

AC:

7031

AN:

29296

Middle Eastern (MID)

AF:

0.210

AC:

548

AN:

2608

European-Non Finnish (NFE)

AF:

0.185

AC:

51720

AN:

279008

Other (OTH)

AF:

0.206

AC:

5427

AN:

26362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

3910

7820

11731

15641

19551

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

400

800

1200

1600

2000

<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:

0.219

AC:

33318

AN:

152182

Hom.:

3811

Cov.:

AF XY:

0.225

AC XY:

16757

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.252

AC:

10467

AN:

41522

American (AMR)

AF:

0.211

AC:

3235

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.118

AC:

409

AN:

3470

East Asian (EAS)

AF:

0.402

AC:

2077

AN:

5166

South Asian (SAS)

AF:

0.281

AC:

1355

AN:

4820

European-Finnish (FIN)

AF:

0.251

AC:

2654

AN:

10576

Middle Eastern (MID)

AF:

0.167

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.184

AC:

12483

AN:

68012

Other (OTH)

AF:

0.226

AC:

476

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1372

2745

4117

5490

6862

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

348

696

1044

1392

1740

<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:

0.199

Hom.:

399

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

(source)

DANN

Benign

0.67

PhyloP100

0.81

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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