Genetic Variant CCT8:c.60+78C>G (chr21-29073453-G-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_006585.4(CCT8):c.60+78C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 1,607,270 control chromosomes in the GnomAD database, including 13,724 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 ( 2209 hom., cov: 33)

Exomes 𝑓: 0.12 ( 11515 hom. )

Consequence

CCT8
NM_006585.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.607

Publications

13 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=-0.8).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCT8	NM_006585.4 link	c.60+78C>G		intron_variant	Intron 1 of 14	ENST00000286788.9	NP_006576.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCT8	ENST00000286788.9 link	c.60+78C>G		intron_variant	Intron 1 of 14	1	NM_006585.4	ENSP00000286788.4

Frequencies

GnomAD3 genomes

AF:

0.157

AC:

23953

AN:

152102

Hom.:

2208

Cov.:

show subpopulations

Gnomad AFR

AF:

0.258

Gnomad AMI

AF:

0.0429

Gnomad AMR

AF:

0.165

Gnomad ASJ

AF:

0.131

Gnomad EAS

AF:

0.147

Gnomad SAS

AF:

0.121

Gnomad FIN

AF:

0.0652

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.115

Gnomad OTH

AF:

0.157

GnomAD4 exome

AF:

0.121

AC:

176551

AN:

1455048

Hom.:

11515

Cov.:

AF XY:

0.120

AC XY:

86735

AN XY:

723352

show subpopulations

African (AFR)

AF:

0.270

AC:

9005

AN:

33370

American (AMR)

AF:

0.176

AC:

7817

AN:

44396

Ashkenazi Jewish (ASJ)

AF:

0.131

AC:

3385

AN:

25932

East Asian (EAS)

AF:

0.103

AC:

4082

AN:

39522

South Asian (SAS)

AF:

0.112

AC:

9644

AN:

85998

European-Finnish (FIN)

AF:

0.0704

AC:

3669

AN:

52152

Middle Eastern (MID)

AF:

0.146

AC:

836

AN:

5728

European-Non Finnish (NFE)

AF:

0.117

AC:

129758

AN:

1107868

Other (OTH)

AF:

0.139

AC:

8355

AN:

60082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

7208

14416

21623

28831

36039

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4860

9720

14580

19440

24300

<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:

0.157

AC:

23973

AN:

152222

Hom.:

2209

Cov.:

AF XY:

0.153

AC XY:

11418

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.258

AC:

10708

AN:

41510

American (AMR)

AF:

0.165

AC:

2520

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.131

AC:

456

AN:

3470

East Asian (EAS)

AF:

0.146

AC:

755

AN:

5168

South Asian (SAS)

AF:

0.121

AC:

582

AN:

4828

European-Finnish (FIN)

AF:

0.0652

AC:

692

AN:

10608

Middle Eastern (MID)

AF:

0.153

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.115

AC:

7842

AN:

68008

Other (OTH)

AF:

0.158

AC:

334

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1026

2052

3077

4103

5129

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

242

484

726

968

1210

<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:

0.144

Hom.:

231

Bravo

AF:

0.169

Asia WGS

AF:

0.149

AC:

520

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.6

(source)

DANN

Benign

0.54

PhyloP100

0.61

PromoterAI

0.090

Neutral

(source)

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