Variant chr22-39134437-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_175709.5(CBX7):c.562G>A(p.Glu188Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000413 in 1,451,418 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

CBX7
NM_175709.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.08

Variant links:

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]

CBX7 links:

CBX7 (HGNC:):

CBX7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13476813).

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CBX7	NM_175709.5 linkuse as main transcript	c.562G>A	p.Glu188Lys	missense_variant	5/6	ENST00000216133.10	NP_783640.1	O95931A0A024R1Q2
CBX7	NM_001346743.2 linkuse as main transcript	c.562G>A	p.Glu188Lys	missense_variant	5/6		NP_001333672.1
CBX7	NM_001346744.2 linkuse as main transcript	c.283G>A	p.Glu95Lys	missense_variant	5/6		NP_001333673.1	Q4PNR6B0QYP2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CBX7	ENST00000216133.10 linkuse as main transcript	c.562G>A	p.Glu188Lys	missense_variant	5/6	1	NM_175709.5	ENSP00000216133.5		O95931

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000129

AC:

AN:

232684

Hom.:

AF XY:

0.0000156

AC XY:

AN XY:

128318

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000329

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000190

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000413

AC:

AN:

1451418

Hom.:

Cov.:

AF XY:

0.00000554

AC XY:

AN XY:

722494

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000828

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 30, 2024

The c.562G>A (p.E188K) alteration is located in exon 5 (coding exon 5) of the CBX7 gene. This alteration results from a G to A substitution at nucleotide position 562, causing the glutamic acid (E) at amino acid position 188 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.041

T;T

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.20

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.85

T;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.7

L;.

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.64

N;N

REVEL

Benign

0.091

Sift

Uncertain

0.021

D;T

Sift4G

Benign

0.27

T;T

Polyphen

0.10

B;P

Vest4

0.23

MutPred

0.23

Gain of ubiquitination at E188 (P = 0.0075);.;

MVP

0.50

MPC

0.38

ClinPred

0.24

GERP RS

2.4

Varity_R

0.16

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over