dbSNP rs2070610: CCT8:n.13C>T (chr21-29073627-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000470450.5(CCT8):n.13C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,602,780 control chromosomes in the GnomAD database, including 14,324 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 0.16 ( 2485 hom., cov: 34)

Exomes 𝑓: 0.12 ( 11839 hom. )

Consequence

CCT8
ENST00000470450.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.337

Publications

27 publications found

Variant links:

Genes affected

CCT8 (HGNC:1623): (chaperonin containing TCP1 subunit 8) This gene encodes the theta subunit of the CCT chaperonin, which is abundant in the eukaryotic cytosol and may be involved in the transport and assembly of newly synthesized proteins. Alternative splicing results in multiple transcript variants of this gene. A pseudogene related to this gene is located on chromosome 1. [provided by RefSeq, Sep 2013]

CCT8 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: G2P
neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

CCT8 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 (AFR) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCT8	NM_006585.4 link	c.-37C>T		5_prime_UTR_variant	Exon 1 of 15	ENST00000286788.9	NP_006576.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCT8	ENST00000286788.9 link	c.-37C>T		5_prime_UTR_variant	Exon 1 of 15	1	NM_006585.4	ENSP00000286788.4

Frequencies

GnomAD3 genomes

AF:

0.165

AC:

25074

AN:

152102

Hom.:

2479

Cov.:

show subpopulations

Gnomad AFR

AF:

0.283

Gnomad AMI

AF:

0.0428

Gnomad AMR

AF:

0.167

Gnomad ASJ

AF:

0.141

Gnomad EAS

AF:

0.147

Gnomad SAS

AF:

0.120

Gnomad FIN

AF:

0.0651

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.115

Gnomad OTH

AF:

0.168

GnomAD2 exomes

AF:

0.137

AC:

34246

AN:

250334

AF XY:

0.131

show subpopulations

Gnomad AFR exome

AF:

0.287

Gnomad AMR exome

AF:

0.180

Gnomad ASJ exome

AF:

0.141

Gnomad EAS exome

AF:

0.160

Gnomad FIN exome

AF:

0.0673

Gnomad NFE exome

AF:

0.118

Gnomad OTH exome

AF:

0.128

GnomAD4 exome

AF:

0.122

AC:

177442

AN:

1450558

Hom.:

11839

Cov.:

AF XY:

0.121

AC XY:

87196

AN XY:

722264

show subpopulations

African (AFR)

AF:

0.297

AC:

9872

AN:

33266

American (AMR)

AF:

0.177

AC:

7910

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.139

AC:

3614

AN:

26070

East Asian (EAS)

AF:

0.103

AC:

4104

AN:

39658

South Asian (SAS)

AF:

0.112

AC:

9644

AN:

86028

European-Finnish (FIN)

AF:

0.0704

AC:

3708

AN:

52682

Middle Eastern (MID)

AF:

0.146

AC:

822

AN:

5638

European-Non Finnish (NFE)

AF:

0.117

AC:

129272

AN:

1102528

Other (OTH)

AF:

0.142

AC:

8496

AN:

59988

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

7756

15512

23267

31023

38779

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4828

9656

14484

19312

24140

<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:

0.165

AC:

25104

AN:

152222

Hom.:

2485

Cov.:

AF XY:

0.160

AC XY:

11932

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.283

AC:

11741

AN:

41510

American (AMR)

AF:

0.167

AC:

2555

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.141

AC:

491

AN:

3472

East Asian (EAS)

AF:

0.147

AC:

759

AN:

5168

South Asian (SAS)

AF:

0.120

AC:

580

AN:

4830

European-Finnish (FIN)

AF:

0.0651

AC:

691

AN:

10618

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.115

AC:

7846

AN:

68010

Other (OTH)

AF:

0.168

AC:

355

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1092

2184

3276

4368

5460

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

250

500

750

1000

1250

<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:

0.138

Hom.:

2172

Bravo

AF:

0.177

Asia WGS

AF:

0.152

AC:

529

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

6.7

(source)

DANN

Benign

0.83

PhyloP100

-0.34

PromoterAI

-0.11

Neutral

(source)

Mutation Taster

=295/5

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