Genetic Variant NM_020649.3:c.982G>C (chr17-79794823-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_020649.3(CBX8):c.982G>C(p.Gly328Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000174 in 1,610,292 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

CBX8
NM_020649.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.27

Publications

0 publications found

Variant links:

Genes affected

CBX8 (HGNC:15962): (chromobox 8) Enables methylated histone binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in chromatin and nucleoplasm. Part of PRC1 complex. Biomarker of esophagus squamous cell carcinoma and glioblastoma. [provided by Alliance of Genome Resources, Apr 2022]

CBX8 Gene-Disease associations (from GenCC):

schizophrenia
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

CBX8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1721679).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020649.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBX8	NM_020649.3	MANE Select	c.982G>C	p.Gly328Arg	missense	Exon 5 of 5	NP_065700.1	Q9HC52

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBX8	ENST00000269385.9	TSL:1 MANE Select	c.982G>C	p.Gly328Arg	missense	Exon 5 of 5	ENSP00000269385.4	Q9HC52
	CBX8	ENST00000413392.5	TSL:3	c.*226G>C		downstream_gene	N/A	ENSP00000405058.1	C9J6K3

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000247

AC:

AN:

242910

AF XY:

0.0000377

show subpopulations

Gnomad AFR exome

AF:

0.000336

Gnomad AMR exome

AF:

0.0000297

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000110

AC:

AN:

1458172

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

725532

show subpopulations

African (AFR)

AF:

0.000211

AC:

AN:

33242

American (AMR)

AF:

0.0000227

AC:

AN:

44042

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25896

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.0000116

AC:

AN:

85940

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52974

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5714

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1110538

Other (OTH)

AF:

0.0000831

AC:

AN:

60140

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000789

AC:

AN:

152120

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.000217

AC:

AN:

41448

American (AMR)

AF:

0.000196

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67988

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.000110

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.57

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.063

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.026

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.5

PhyloP100

5.3

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.66

REVEL

Benign

0.15

Sift

Uncertain

0.0040

Sift4G

Benign

0.55

Polyphen

0.99

Vest4

0.17

MutPred

0.21

Gain of MoRF binding (P = 0.0206)

MVP

0.48

MPC

0.84

ClinPred

0.19

GERP RS

5.0

Varity_R

0.33

gMVP

0.45

Mutation Taster

=82/18

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over