Genetic Variant CCT8:c.1569+305C>T (chr21-29060236-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 NM_006585.4(CCT8):c.1569+305C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 182,016 control chromosomes in the GnomAD database, including 2,476 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 ( 2251 hom., cov: 32)

Exomes 𝑓: 0.11 ( 225 hom. )

Consequence

CCT8
NM_006585.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.617

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:

ENSG00000231125 (HGNC:):

ENSG00000231125 links:

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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=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCT8	NM_006585.4 link	c.1569+305C>T		intron_variant	Intron 14 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.1569+305C>T		intron_variant	Intron 14 of 14	1	NM_006585.4	ENSP00000286788.4

Frequencies

GnomAD3 genomes

AF:

0.158

AC:

24036

AN:

151928

Hom.:

2249

Cov.:

show subpopulations

Gnomad AFR

AF:

0.261

Gnomad AMI

AF:

0.0428

Gnomad AMR

AF:

0.165

Gnomad ASJ

AF:

0.132

Gnomad EAS

AF:

0.145

Gnomad SAS

AF:

0.118

Gnomad FIN

AF:

0.0651

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.115

Gnomad OTH

AF:

0.156

GnomAD4 exome

AF:

0.108

AC:

3248

AN:

29970

Hom.:

225

AF XY:

0.105

AC XY:

1696

AN XY:

16078

show subpopulations

African (AFR)

AF:

0.268

AC:

226

AN:

844

American (AMR)

AF:

0.154

AC:

179

AN:

1162

Ashkenazi Jewish (ASJ)

AF:

0.0983

AC:

103

AN:

1048

East Asian (EAS)

AF:

0.0647

AC:

101

AN:

1560

South Asian (SAS)

AF:

0.107

AC:

199

AN:

1868

European-Finnish (FIN)

AF:

0.0572

AC:

AN:

1102

Middle Eastern (MID)

AF:

0.175

AC:

AN:

114

European-Non Finnish (NFE)

AF:

0.105

AC:

2148

AN:

20452

Other (OTH)

AF:

0.115

AC:

209

AN:

1820

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

144

288

431

575

719

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.158

AC:

24058

AN:

152046

Hom.:

2251

Cov.:

AF XY:

0.154

AC XY:

11469

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.261

AC:

10824

AN:

41460

American (AMR)

AF:

0.165

AC:

2520

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.132

AC:

457

AN:

3472

East Asian (EAS)

AF:

0.145

AC:

751

AN:

5184

South Asian (SAS)

AF:

0.118

AC:

568

AN:

4818

European-Finnish (FIN)

AF:

0.0651

AC:

687

AN:

10558

Middle Eastern (MID)

AF:

0.153

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.115

AC:

7836

AN:

67972

Other (OTH)

AF:

0.157

AC:

331

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

976

1953

2929

3906

4882

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

244

488

732

976

1220

<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:

0.145

Hom.:

523

Bravo

AF:

0.170

Asia WGS

AF:

0.148

AC:

518

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.7

(source)

DANN

Benign

0.27

PhyloP100

0.62

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