rs1063192

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 1P and 9B. PP5BP4BA1

The NM_004936.4(CDKN2B):c.*2619C>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 0.689 in 223,992 control chromosomes in the GnomAD database, including 55,584 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic,protective (no stars).

Frequency

Genomes: 𝑓 0.71 ( 39900 hom., cov: 33)

Exomes 𝑓: 0.65 ( 15684 hom. )

Consequence

CDKN2B
NM_004936.4 3_prime_UTR

Scores

Clinical Significance

Likely pathogenic; protective no assertion criteria provided P:1B:1O:1

Conservation

PhyloP100: -2.17

Publications

180 publications found

Variant links:

Genes affected

CDKN2B (HGNC:1788): (cyclin dependent kinase inhibitor 2B) This gene lies adjacent to the tumor suppressor gene CDKN2A in a region that is frequently mutated and deleted in a wide variety of tumors. This gene encodes a cyclin-dependent kinase inhibitor, which forms a complex with CDK4 or CDK6, and prevents the activation of the CDK kinases, thus the encoded protein functions as a cell growth regulator that controls cell cycle G1 progression. The expression of this gene was found to be dramatically induced by TGF beta, which suggested its role in the TGF beta induced growth inhibition. Two alternatively spliced transcript variants of this gene, which encode distinct proteins, have been reported. [provided by RefSeq, Jul 2008]

CDKN2B links:

CDKN2B-AS1 (HGNC:34341): (CDKN2B antisense RNA 1) This gene is located within the CDKN2B-CDKN2A gene cluster at chromosome 9p21. The gene product is a functional RNA molecule that interacts with polycomb repressive complex-1 (PRC1) and -2 (PRC2), leading to epigenetic silencing of other genes in this cluster. This region is a significant genetic susceptibility locus for cardiovascular disease, and has also been linked to a number of other pathologies, including several cancers, intracranial aneurysm, type-2 diabetes, periodontitis, Alzheimer's disease, endometriosis, frailty in the elderly, and glaucoma. Multiple alternatively processed transcript variants have been detected, some of which may take the form of circular RNA molecules (PMID:21151960). [provided by RefSeq, May 2014]

CDKN2B-AS1 links:

ENSG00000264545 (HGNC:):

ENSG00000264545 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

PP5

Variant 9-22003368-G-A is Pathogenic according to our data. Variant chr9-22003368-G-A is described in ClinVar as Likely_pathogenic|protective. ClinVar VariationId is 812639.Status of the report is no_assertion_criteria_provided, 0 stars.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91). . Strength limited to SUPPORTING due to the PP5.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.916 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN2B	NM_004936.4 link	c.*2619C>T		3_prime_UTR_variant	Exon 2 of 2	ENST00000276925.7	NP_004927.2	P42772-1K7PPU3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN2B	ENST00000276925.7 link	c.*2619C>T		3_prime_UTR_variant	Exon 2 of 2	1	NM_004936.4	ENSP00000276925.6		P42772-1

Frequencies

GnomAD3 genomes

AF:

0.707

AC:

107346

AN:

151824

Hom.:

39840

Cov.:

show subpopulations

Gnomad AFR

AF:

0.924

Gnomad AMI

AF:

0.504

Gnomad AMR

AF:

0.779

Gnomad ASJ

AF:

0.715

Gnomad EAS

AF:

0.821

Gnomad SAS

AF:

0.749

Gnomad FIN

AF:

0.576

Gnomad MID

AF:

0.825

Gnomad NFE

AF:

0.568

Gnomad OTH

AF:

0.726

GnomAD4 exome

AF:

0.652

AC:

46963

AN:

72050

Hom.:

15684

Cov.:

AF XY:

0.650

AC XY:

21674

AN XY:

33328

show subpopulations

African (AFR)

AF:

0.931

AC:

3219

AN:

3456

American (AMR)

AF:

0.786

AC:

1727

AN:

2198

Ashkenazi Jewish (ASJ)

AF:

0.713

AC:

3249

AN:

4558

East Asian (EAS)

AF:

0.793

AC:

7916

AN:

9988

South Asian (SAS)

AF:

0.713

AC:

456

AN:

640

European-Finnish (FIN)

AF:

0.625

AC:

AN:

Middle Eastern (MID)

AF:

0.776

AC:

332

AN:

428

European-Non Finnish (NFE)

AF:

0.582

AC:

25993

AN:

44648

Other (OTH)

AF:

0.664

AC:

4036

AN:

6078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

754

1508

2263

3017

3771

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

106

212

318

424

530

<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:

0.707

AC:

107459

AN:

151942

Hom.:

39900

Cov.:

AF XY:

0.708

AC XY:

52586

AN XY:

74242

show subpopulations

African (AFR)

AF:

0.924

AC:

38393

AN:

41550

American (AMR)

AF:

0.780

AC:

11909

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.715

AC:

2477

AN:

3462

East Asian (EAS)

AF:

0.821

AC:

4244

AN:

5168

South Asian (SAS)

AF:

0.749

AC:

3618

AN:

4828

European-Finnish (FIN)

AF:

0.576

AC:

6077

AN:

10548

Middle Eastern (MID)

AF:

0.825

AC:

241

AN:

292

European-Non Finnish (NFE)

AF:

0.568

AC:

38520

AN:

67796

Other (OTH)

AF:

0.720

AC:

1522

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1468

2936

4405

5873

7341

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

814

1628

2442

3256

4070

<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:

0.611

Hom.:

132370

Bravo

AF:

0.729

Asia WGS

AF:

0.758

AC:

2629

AN:

3470

ClinVar

Significance: Likely pathogenic; protective

Submissions summary: Pathogenic:1Benign:1Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Malignant tumor of breast

Pathogenic:1

Jul 01, 2023

Institute of Biochemistry And Biotechnology, University of Veterinary and Animal Sciences, Lahore, Pakistan

Significance:Likely pathogenic

Review Status:no assertion criteria provided

Collection Method:research

- -

Three Vessel Coronary Disease

Benign:1

Department of Cardiology, Chinese Academy of Medical Sciences, Fuwai Hospital

Significance:protective

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Neoplasm

Other:1

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance:-

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.38

(source)

DANN

Benign

0.63

PhyloP100

-2.2

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over