Genetic Variant CBX1:c.319-97G>T (chr17-48075197-C-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.319-97G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 634,236 control chromosomes in the GnomAD database, including 3,318 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 0.16 ( 2492 hom., cov: 30)

Exomes 𝑓: 0.10 ( 826 hom. )

Consequence

CBX1
NM_001127228.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.128

Publications

15 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=-0.76).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CBX1	NM_001127228.2 link	c.319-97G>T		intron_variant	Intron 3 of 4	ENST00000225603.9	NP_001120700.1	P83916Q6IBN6
CBX1	NM_006807.5 link	c.319-97G>T		intron_variant	Intron 3 of 4		NP_006798.1	P83916Q6IBN6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CBX1	ENST00000225603.9 link	c.319-97G>T		intron_variant	Intron 3 of 4	1	NM_001127228.2	ENSP00000225603.4		P83916

Frequencies

GnomAD3 genomes

AF:

0.162

AC:

23598

AN:

145962

Hom.:

2492

Cov.:

show subpopulations

Gnomad AFR

AF:

0.296

Gnomad AMI

AF:

0.0902

Gnomad AMR

AF:

0.112

Gnomad ASJ

AF:

0.131

Gnomad EAS

AF:

0.00120

Gnomad SAS

AF:

0.0988

Gnomad FIN

AF:

0.122

Gnomad MID

AF:

0.153

Gnomad NFE

AF:

0.116

Gnomad OTH

AF:

0.161

GnomAD4 exome

AF:

0.103

AC:

50068

AN:

488212

Hom.:

826

AF XY:

0.104

AC XY:

26784

AN XY:

258448

show subpopulations

African (AFR)

AF:

0.243

AC:

2998

AN:

12348

American (AMR)

AF:

0.0802

AC:

1643

AN:

20498

Ashkenazi Jewish (ASJ)

AF:

0.117

AC:

1621

AN:

13834

East Asian (EAS)

AF:

0.0205

AC:

586

AN:

28558

South Asian (SAS)

AF:

0.105

AC:

4738

AN:

45280

European-Finnish (FIN)

AF:

0.120

AC:

4395

AN:

36594

Middle Eastern (MID)

AF:

0.150

AC:

502

AN:

3350

European-Non Finnish (NFE)

AF:

0.102

AC:

30918

AN:

302420

Other (OTH)

AF:

0.105

AC:

2667

AN:

25330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.428

Heterozygous variant carriers

1606

3212

4817

6423

8029

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

414

828

1242

1656

2070

<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:

0.162

AC:

23614

AN:

146024

Hom.:

2492

Cov.:

AF XY:

0.157

AC XY:

11151

AN XY:

70906

show subpopulations

African (AFR)

AF:

0.296

AC:

11902

AN:

40238

American (AMR)

AF:

0.111

AC:

1616

AN:

14516

Ashkenazi Jewish (ASJ)

AF:

0.131

AC:

446

AN:

3400

East Asian (EAS)

AF:

0.00121

AC:

AN:

4978

South Asian (SAS)

AF:

0.0985

AC:

452

AN:

4590

European-Finnish (FIN)

AF:

0.122

AC:

1131

AN:

9274

Middle Eastern (MID)

AF:

0.142

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.116

AC:

7624

AN:

65866

Other (OTH)

AF:

0.159

AC:

317

AN:

1998

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

883

1767

2650

3534

4417

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

240

480

720

960

1200

<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:

0.200

Hom.:

1742

Bravo

AF:

0.275

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

1.8

(source)

DANN

Benign

0.87

PhyloP100

0.13

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over