chr22-39134031-C-T

Variant names:

• chr22-39134031-C-T
• rs758040396
• NM_175709.5:c.616G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_175709.5(CBX7):​c.616G>A​(p.Glu206Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000015 in 1,603,332 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: CBX7 NM_175709.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.29
• Publications: 1 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07637969).
• BS2: High AC in GnomAdExome4 at 23 AD gene.

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.616G>A	p.Glu206Lys	missense	Exon 6 of 6	NP_783640.1	O95931
	CBX7	NM_001346743.2		c.613G>A	p.Glu205Lys	missense	Exon 6 of 6	NP_001333672.1
	CBX7	NM_001346744.2		c.337G>A	p.Glu113Lys	missense	Exon 6 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.616G>A	p.Glu206Lys	missense	Exon 6 of 6	ENSP00000216133.5	O95931
	CBX7	ENST00000401405.7	TSL:1	c.337G>A	p.Glu113Lys	missense	Exon 6 of 6	ENSP00000384035.3	B0QYP2
	CBX7	ENST00000858784.1		c.694G>A	p.Glu232Lys	missense	Exon 7 of 7	ENSP00000528843.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152140 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000122 AC: 3 AN: 246450 AF XY: 0.0000150

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000296

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000553

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000158 AC: 23 AN: 1451192 Hom.: 0 Cov.: 31 AF XY: 0.0000194 AC XY: 14 AN XY: 720452

African (AFR) AF: 0.0000301 AC: 1 AN: 33186

American (AMR) AF: 0.0000228 AC: 1 AN: 43912

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25888

East Asian (EAS) AF: 0.0000508 AC: 2 AN: 39372

South Asian (SAS) AF: 0.0000350 AC: 3 AN: 85772

European-Finnish (FIN) AF: 0.0000189 AC: 1 AN: 52952

Middle Eastern (MID) AF: 0.000204 AC: 1 AN: 4894

European-Non Finnish (NFE) AF: 0.00000905 AC: 10 AN: 1105456

Other (OTH) AF: 0.0000669 AC: 4 AN: 59760

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152140 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74334

African (AFR) AF: 0.0000241 AC: 1 AN: 41434

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000165 AC: 2

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		1.3
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.53	N
REVEL	Benign	0.025
Sift	Benign	0.087	T
Sift4G	Benign	0.26	T
Polyphen		0.10	B
Vest4		0.047
MutPred		0.30		Gain of ubiquitination at E206 (P = 0.0039)
MVP		0.25
MPC		0.38
ClinPred		0.18	T
GERP RS		4.1
Varity_R		0.059
gMVP		0.34
Mutation Taster		=90/10	polymorphism

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: rs758040396; hg19: chr22-39530036; COSMIC: COSV104574043; COSMIC: COSV104574043;