Variant chr17-34942908-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 3P and 6B. PVS1_ModeratePP3BP6_ModerateBS2

The NM_006584.4(CCT6B):c.615-2A>G variant causes a splice acceptor change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00523 in 1,490,326 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0035 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0054 ( 21 hom. )

Consequence

CCT6B
NM_006584.4 splice_acceptor

Scores

Splicing: ADA: 1.000

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.43

Variant links:

Genes affected

CCT6B (HGNC:1621): (chaperonin containing TCP1 subunit 6B) This gene encodes 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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2015]

CCT6B links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.0690521 fraction of the gene. Cryptic splice site detected, with MaxEntScore 4.9, offset of -40, new splice context is: aattttataccaaattttAGagt. Cryptic site results in frameshift change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.

PP3

Multiple lines of computational evidence support a deleterious effect 6: BayesDel_noAF, Cadd, dbscSNV1_ADA, dbscSNV1_RF, max_spliceai, Eigen [when BayesDel_addAF, MutationTaster was below the threshold]

BP6

Variant 17-34942908-T-C is Benign according to our data. Variant chr17-34942908-T-C is described in ClinVar as [Benign]. Clinvar id is 778127.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
CCT6B	NM_006584.4 linkuse as main transcript	c.615-2A>G	splice_acceptor_variant	ENST00000314144.10
CCT6B	NM_001193530.2 linkuse as main transcript	c.480-2A>G	splice_acceptor_variant
CCT6B	NM_001193529.3 linkuse as main transcript	c.615-265A>G	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCT6B	ENST00000314144.10 linkuse as main transcript	c.615-2A>G		splice_acceptor_variant		1	NM_006584.4	P1	Q92526-1

Frequencies

GnomAD3 genomes

AF:

0.00353

AC:

538

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00128

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.000961

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00633

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00397

AC:

780

AN:

196672

Hom.:

AF XY:

0.00391

AC XY:

415

AN XY:

106232

show subpopulations

Gnomad AFR exome

AF:

0.00129

Gnomad AMR exome

AF:

0.00141

Gnomad ASJ exome

AF:

0.00205

Gnomad EAS exome

AF:

0.000275

Gnomad SAS exome

AF:

0.000418

Gnomad FIN exome

AF:

0.00285

Gnomad NFE exome

AF:

0.00719

Gnomad OTH exome

AF:

0.00385

GnomAD4 exome

AF:

0.00542

AC:

7250

AN:

1337982

Hom.:

Cov.:

AF XY:

0.00527

AC XY:

3524

AN XY:

668532

show subpopulations

Gnomad4 AFR exome

AF:

0.000944

Gnomad4 AMR exome

AF:

0.00132

Gnomad4 ASJ exome

AF:

0.00218

Gnomad4 EAS exome

AF:

0.00190

Gnomad4 SAS exome

AF:

0.000371

Gnomad4 FIN exome

AF:

0.00281

Gnomad4 NFE exome

AF:

0.00652

Gnomad4 OTH exome

AF:

0.00416

GnomAD4 genome

AF:

0.00353

AC:

538

AN:

152344

Hom.:

Cov.:

AF XY:

0.00350

AC XY:

261

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.00127

Gnomad4 AMR

AF:

0.000653

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.000963

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00188

Gnomad4 NFE

AF:

0.00634

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00585

Hom.:

Bravo

AF:

0.00340

TwinsUK

AF:

0.00512

AC:

ALSPAC

AF:

0.00804

AC:

ESP6500AA

AF:

0.000909

AC:

ESP6500EA

AF:

0.00698

AC:

ExAC

AF:

0.00336

AC:

406

Asia WGS

AF:

0.000578

AC:

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.036

BayesDel_noAF

Pathogenic

0.19

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Pathogenic

0.97

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Uncertain

0.96

MutationTaster

Benign

1.0

D;D;D

GERP RS

4.2

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.93

SpliceAI score (max)

0.99

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.61

Position offset: -13

DS_AL_spliceai

0.99

Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over