rs8066940

Positions:

• chr17-79792822-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000269385.9(CBX8):​c.*1813C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 151,966 control chromosomes in the GnomAD database, including 14,542 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 0.41 (14541 hom., cov: 30)
  • Exomes 𝑓: 0.33 (1 hom.)
• Consequence: CBX8 ENST00000269385.9 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.381

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CBX8	NM_020649.3	c.*1813C>T		3_prime_UTR_variant	5/5	ENST00000269385.9	NP_065700.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CBX8	ENST00000269385.9	c.*1813C>T		3_prime_UTR_variant	5/5	1	NM_020649.3	ENSP00000269385	P1

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62560 AN: 151844 Hom.: 14490 Cov.: 30

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.376

GnomAD4 exome AF: 0.333 AC: 2 AN: 6 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

Gnomad4 NFE exome AF: 0.333

GnomAD4 genome AF: 0.412 AC: 62663 AN: 151960 Hom.: 14541 Cov.: 30 AF XY: 0.409 AC XY: 30339 AN XY: 74266

Gnomad4 AFR AF: 0.638

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.351

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.469

Gnomad4 FIN AF: 0.282

Gnomad4 NFE AF: 0.337

Gnomad4 OTH AF: 0.380

Alfa AF: 0.346 Hom.: 13785

Bravo AF: 0.417

Asia WGS AF: 0.374 AC: 1304 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	12
DANN	Benign	0.90

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

LitVar

Other links and lift over

dbSNP: rs8066940; hg19: chr17-77766621;