rs748996167

Variant names:

• chr17-79795332-C-A
• rs748996167
• NM_020649.3:c.473G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-79795332-C-A
• chr17-79795332-C-G
• chr17-79795332-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020649.3(CBX8):​c.473G>T​(p.Arg158Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000021 in 1,431,400 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R158Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CBX8 NM_020649.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.89
• Publications: 0 publications found

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)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.075936586).

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.473G>T	p.Arg158Leu	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.473G>T	p.Arg158Leu	missense	Exon 5 of 5	ENSP00000269385.4	Q9HC52
	CBX8	ENST00000413392.5	TSL:3	c.443G>T	p.Arg148Leu	missense	Exon 5 of 5	ENSP00000405058.1	C9J6K3
	CBX8	ENST00000427800.2	TSL:2	c.398G>T	p.Arg133Leu	missense	Exon 5 of 5	ENSP00000408753.2	C9JM54

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000195 AC: 4 AN: 204808 AF XY: 0.0000183

Gnomad AFR exome AF: 0.000154

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000111

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000210 AC: 3 AN: 1431400 Hom.: 0 Cov.: 35 AF XY: 0.00000141 AC XY: 1 AN XY: 709586

African (AFR) AF: 0.00 AC: 0 AN: 33202

American (AMR) AF: 0.00 AC: 0 AN: 39310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25450

East Asian (EAS) AF: 0.00 AC: 0 AN: 38588

South Asian (SAS) AF: 0.0000242 AC: 2 AN: 82674

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51326

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1095640

Other (OTH) AF: 0.0000168 AC: 1 AN: 59474

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.067	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.66
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.9
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.039
Sift	Benign	0.13	T
Sift4G	Benign	0.80	T
Polyphen		0.25	B
Vest4		0.36
MutPred		0.28		Loss of MoRF binding (P = 0.0659)
MVP		0.41
MPC		0.26
ClinPred		0.034	T
GERP RS		2.3
Varity_R		0.089
gMVP		0.25
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs748996167; hg19: chr17-77769131; COSMIC: COSV99485865; COSMIC: COSV99485865;