dbSNP rs6847: CBX1:c.*990A>T (chr17-48070445-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001127228.2(CBX1):c.*990A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 152,502 control chromosomes in the GnomAD database, including 6,385 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 0.27 ( 6374 hom., cov: 32)

Exomes 𝑓: 0.21 ( 11 hom. )

Consequence

CBX1
NM_001127228.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.678

Publications

17 publications found

Variant links:

Genes affected

CBX1 (HGNC:1551): (chromobox 1) This gene encodes a highly conserved nonhistone protein, which is a member of the heterochromatin protein family . The protein is enriched in the heterochromatin and associated with centromeres. The protein has a single N-terminal chromodomain which can bind to histone proteins via methylated lysine residues, and a C-terminal chromo shadow-domain (CSD) which is responsible for the homodimerization and interaction with a number of chromatin-associated nonhistone proteins. The protein may play an important role in the epigenetic control of chromatin structure and gene expression. Several related pseudogenes are located on chromosomes 1, 3, and X. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jul 2008]

CBX1 Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AD Classification: MODERATE Submitted by: G2P

CBX1 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=-0.82).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CBX1	NM_001127228.2 link	c.*990A>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000225603.9	NP_001120700.1	P83916Q6IBN6
CBX1	NM_006807.5 link	c.*990A>T		3_prime_UTR_variant	Exon 5 of 5		NP_006798.1	P83916Q6IBN6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CBX1	ENST00000225603.9 link	c.*990A>T		3_prime_UTR_variant	Exon 5 of 5	1	NM_001127228.2	ENSP00000225603.4		P83916
CBX1	ENST00000393408.7 link	c.*990A>T		3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000377060.3		P83916

Frequencies

GnomAD3 genomes

AF:

0.273

AC:

41411

AN:

151944

Hom.:

6366

Cov.:

show subpopulations

Gnomad AFR

AF:

0.426

Gnomad AMI

AF:

0.285

Gnomad AMR

AF:

0.185

Gnomad ASJ

AF:

0.220

Gnomad EAS

AF:

0.191

Gnomad SAS

AF:

0.207

Gnomad FIN

AF:

0.238

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.218

Gnomad OTH

AF:

0.250

GnomAD4 exome

AF:

0.207

AC:

AN:

440

Hom.:

Cov.:

AF XY:

0.225

AC XY:

AN XY:

262

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.211

AC:

AN:

426

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.125

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.273

AC:

41444

AN:

152062

Hom.:

6374

Cov.:

AF XY:

0.267

AC XY:

19884

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.426

AC:

17639

AN:

41450

American (AMR)

AF:

0.185

AC:

2822

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.220

AC:

764

AN:

3470

East Asian (EAS)

AF:

0.191

AC:

990

AN:

5180

South Asian (SAS)

AF:

0.207

AC:

999

AN:

4824

European-Finnish (FIN)

AF:

0.238

AC:

2521

AN:

10578

Middle Eastern (MID)

AF:

0.289

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.218

AC:

14838

AN:

67978

Other (OTH)

AF:

0.250

AC:

527

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1453

2905

4358

5810

7263

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

412

824

1236

1648

2060

<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:

0.247

Hom.:

676

Bravo

AF:

0.276

Asia WGS

AF:

0.191

AC:

667

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.2

(source)

DANN

Benign

0.66

PhyloP100

0.68

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over