rs769000260

Variant names:

• chr22-39134437-C-A
• rs769000260
• NM_175709.5:c.562G>T

Your query was ambiguous. Multiple possible variants found:

• chr22-39134437-C-A
• chr22-39134437-C-T

Variant summary

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

The NM_175709.5(CBX7):​c.562G>T​(p.Glu188*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000689 in 1,451,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CBX7 NM_175709.5 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.08
• Publications: 0 publications found

Genes affected

CBX7 (HGNC:1557): (chromobox 7) This gene encodes a protein that contains the CHROMO (CHRomatin Organization MOdifier) domain. The encoded protein is a component of the Polycomb repressive complex 1 (PRC1), and is thought to control the lifespan of several normal human cells. [provided by RefSeq, Oct 2016]

ENSG00000279833 (HGNC:58395):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175709.5. 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
	CBX7	NM_175709.5	MANE Select	c.562G>T	p.Glu188*	stop_gained	Exon 5 of 6	NP_783640.1	O95931
	CBX7	NM_001346743.2		c.562G>T	p.Glu188*	stop_gained	Exon 5 of 6	NP_001333672.1
	CBX7	NM_001346744.2		c.283G>T	p.Glu95*	stop_gained	Exon 5 of 6	NP_001333673.1	B0QYP2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBX7	ENST00000216133.10	TSL:1 MANE Select	c.562G>T	p.Glu188*	stop_gained	Exon 5 of 6	ENSP00000216133.5	O95931
	CBX7	ENST00000401405.7	TSL:1	c.283G>T	p.Glu95*	stop_gained	Exon 5 of 6	ENSP00000384035.3	B0QYP2
	CBX7	ENST00000858784.1		c.640G>T	p.Glu214*	stop_gained	Exon 6 of 7	ENSP00000528843.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1451416 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 722492

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44650

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86124

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44000

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5614

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111594

Other (OTH) AF: 0.00 AC: 0 AN: 60198

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.57	D
BayesDel_noAF	Pathogenic	0.59
CADD	Pathogenic	37
DANN	Uncertain	1.0
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.97	D
PhyloP100		4.1
Vest4		0.82
GERP RS		2.4
Mutation Taster		=26/174	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs769000260; hg19: chr22-39530442; COSMIC: COSV99334123; COSMIC: COSV99334123;