chr17-79792822-G-A

Variant names:

• chr17-79792822-G-A
• rs8066940
• NM_020649.3:c.*1813C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020649.3(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 NM_020649.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.381
• Publications: 4 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
CBX8	NM_020649.3	c.*1813C>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000269385.9	NP_065700.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CBX8	ENST00000269385.9	c.*1813C>T		3_prime_UTR_variant	Exon 5 of 5	1	NM_020649.3	ENSP00000269385.4

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.333 AC: 2 AN: 6

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.638 AC: 26420 AN: 41414

American (AMR) AF: 0.307 AC: 4687 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1219 AN: 3472

East Asian (EAS) AF: 0.204 AC: 1050 AN: 5146

South Asian (SAS) AF: 0.469 AC: 2258 AN: 4814

European-Finnish (FIN) AF: 0.282 AC: 2971 AN: 10554

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.337 AC: 22922 AN: 67958

Other (OTH) AF: 0.380 AC: 801 AN: 2110

Alfa AF: 0.353 Hom.: 19968

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
PhyloP100		0.38
Mutation Taster		=100/0	polymorphism (auto)

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: rs8066940; hg19: chr17-77766621;