Genetic Variant CBX7:p.Ala214Thr (chr22-39134007-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_175709.5(CBX7):c.640G>A(p.Ala214Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000959 in 1,459,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A214V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

CBX7
NM_175709.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.492

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:

ENSG00000279833 (HGNC:):

ENSG00000279833 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012862891).

BP6

Variant 22-39134007-C-T is Benign according to our data. Variant chr22-39134007-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3827949.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CBX7	NM_175709.5 link	c.640G>A	p.Ala214Thr	missense_variant	Exon 6 of 6	ENST00000216133.10	NP_783640.1	O95931A0A024R1Q2
CBX7	NM_001346743.2 link	c.637G>A	p.Ala213Thr	missense_variant	Exon 6 of 6		NP_001333672.1
CBX7	NM_001346744.2 link	c.361G>A	p.Ala121Thr	missense_variant	Exon 6 of 6		NP_001333673.1	Q4PNR6B0QYP2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CBX7	ENST00000216133.10 link	c.640G>A	p.Ala214Thr	missense_variant	Exon 6 of 6	1	NM_175709.5	ENSP00000216133.5		O95931

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000480

AC:

AN:

250158

Hom.:

AF XY:

0.0000370

AC XY:

AN XY:

135314

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000348

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000959

AC:

AN:

1459546

Hom.:

Cov.:

AF XY:

0.00000827

AC XY:

AN XY:

725802

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000314

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Feb 27, 2025

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.75

CADD

Benign

8.1

DANN

Benign

0.90

DEOGEN2

Benign

0.026

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.73

T;T

M_CAP

Benign

0.0027

MetaRNN

Benign

0.013

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.18

N;.

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.33

N;N

REVEL

Benign

0.15

Sift

Benign

0.63

T;T

Sift4G

Benign

0.72

T;T

Polyphen

0.0

B;B

Vest4

0.020

MutPred

0.13

Gain of glycosylation at A214 (P = 0.0012);.;

MVP

0.25

MPC

0.31

ClinPred

0.012

GERP RS

-8.0

Varity_R

0.055

gMVP

0.18

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

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