rs193920857

Positions:

• chr22-39138655-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_175709.5(CBX7):​c.227C>G​(p.Pro76Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CBX7 NM_175709.5 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 7.25

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41568035).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CBX7	NM_175709.5	c.227C>G	p.Pro76Arg	missense_variant	4/6	ENST00000216133.10	NP_783640.1
CBX7	NM_001346743.2	c.227C>G	p.Pro76Arg	missense_variant	4/6		NP_001333672.1
CBX7	NM_001346744.2	c.227C>G	p.Pro76Arg	missense_variant	4/6		NP_001333673.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CBX7	ENST00000216133.10	c.227C>G	p.Pro76Arg	missense_variant	4/6	1	NM_175709.5	ENSP00000216133.5
CBX7	ENST00000401405.7	c.227C>G	p.Pro76Arg	missense_variant	4/6	1		ENSP00000384035.3
CBX7	ENST00000434260.1	c.161C>G	p.Pro54Arg	missense_variant	3/4	3		ENSP00000410896.1
CBX7	ENST00000475962.5	n.44+11134C>G		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Science for Life laboratory, Karolinska Institutet

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Uncertain	0.049	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T;T;.
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.42	T;T;T
MetaSVM	Benign	-0.50	T
MutationAssessor	Uncertain	2.4	M;.;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-7.3	D;D;D
REVEL	Benign	0.24
Sift	Uncertain	0.0020	D;T;D
Sift4G	Uncertain	0.0050	D;T;.
Polyphen		0.99	D;D;.
Vest4		0.58
MutPred		0.22		Loss of glycosylation at P76 (P = 0.0077);Loss of glycosylation at P76 (P = 0.0077);.;
MVP		0.45
MPC		1.2
ClinPred		0.99	D
GERP RS		4.8
Varity_R		0.80
gMVP		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs193920857; hg19: chr22-39534660; COSMIC: COSV53358694; COSMIC: COSV53358694;