dbSNP rs3751954: CBX2:n.514A>G (chr17-79779686-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000571484.1(CBX2):n.514A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 531,454 control chromosomes in the GnomAD database, including 3,687 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.10 ( 994 hom., cov: 34)

Exomes 𝑓: 0.11 ( 2693 hom. )

Consequence

CBX2
ENST00000571484.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.198

Publications

2 publications found

Variant links:

Genes affected

CBX2 (HGNC:1552): (chromobox 2) This gene encodes a component of the polycomb multiprotein complex, which is required to maintain the transcriptionally repressive state of many genes throughout development via chromatin remodeling and modification of histones. Disruption of this gene in mice results in male-to-female gonadal sex reversal. Mutations in this gene are also associated with gonadal dysgenesis in humans. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene.[provided by RefSeq, Mar 2010]

CBX2 Gene-Disease associations (from GenCC):

46,XY complete gonadal dysgenesis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
46,XY sex reversal 5
Inheritance: SD, AR Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

CBX2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CBX2	NM_005189.3 link	c.182+259A>G		intron_variant	Intron 3 of 4	ENST00000310942.9	NP_005180.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
CBX2	ENST00000571484.1 link	n.514A>G	non_coding_transcript_exon_variant	Exon 3 of 3	1
CBX2	ENST00000310942.9 link	c.182+259A>G	intron_variant	Intron 3 of 4	1	NM_005189.3	ENSP00000308750.4
CBX2	ENST00000269399.5 link	c.182+259A>G	intron_variant	Intron 3 of 3	1		ENSP00000269399.5

Frequencies

GnomAD3 genomes

AF:

0.101

AC:

15354

AN:

152180

Hom.:

987

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0486

Gnomad AMI

AF:

0.0824

Gnomad AMR

AF:

0.182

Gnomad ASJ

AF:

0.0700

Gnomad EAS

AF:

0.102

Gnomad SAS

AF:

0.0959

Gnomad FIN

AF:

0.163

Gnomad MID

AF:

0.0318

Gnomad NFE

AF:

0.107

Gnomad OTH

AF:

0.102

GnomAD4 exome

AF:

0.112

AC:

42554

AN:

379156

Hom.:

2693

Cov.:

AF XY:

0.111

AC XY:

22024

AN XY:

198336

show subpopulations

African (AFR)

AF:

0.0480

AC:

536

AN:

11172

American (AMR)

AF:

0.236

AC:

4001

AN:

16950

Ashkenazi Jewish (ASJ)

AF:

0.0734

AC:

867

AN:

11812

East Asian (EAS)

AF:

0.0947

AC:

2553

AN:

26946

South Asian (SAS)

AF:

0.0886

AC:

3473

AN:

39194

European-Finnish (FIN)

AF:

0.160

AC:

3785

AN:

23696

Middle Eastern (MID)

AF:

0.0438

AC:

AN:

1668

European-Non Finnish (NFE)

AF:

0.110

AC:

24886

AN:

225492

Other (OTH)

AF:

0.107

AC:

2380

AN:

22226

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1749

3497

5246

6994

8743

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

174

348

522

696

870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.101

AC:

15377

AN:

152298

Hom.:

994

Cov.:

AF XY:

0.104

AC XY:

7723

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.0484

AC:

2014

AN:

41576

American (AMR)

AF:

0.182

AC:

2791

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0700

AC:

243

AN:

3472

East Asian (EAS)

AF:

0.102

AC:

527

AN:

5178

South Asian (SAS)

AF:

0.0968

AC:

467

AN:

4824

European-Finnish (FIN)

AF:

0.163

AC:

1727

AN:

10614

Middle Eastern (MID)

AF:

0.0342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.107

AC:

7299

AN:

68016

Other (OTH)

AF:

0.106

AC:

224

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

729

1458

2188

2917

3646

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

328

492

656

820

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.105

Hom.:

760

Bravo

AF:

0.105

Asia WGS

AF:

0.111

AC:

385

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.3

(source)

DANN

Benign

0.84

PhyloP100

-0.20

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over