rs2069426

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004936.4(CDKN2B):c.157-27C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0853 in 1,600,488 control chromosomes in the GnomAD database, including 6,023 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.087 ( 573 hom., cov: 33)

Exomes 𝑓: 0.085 ( 5450 hom. )

Consequence

CDKN2B
NM_004936.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0560

Publications

25 publications found

Variant links:

COSMIC-nc: COSV99439453

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 -20 ACMG points.

BP4

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

BP6

Variant 9-22006274-G-T is Benign according to our data. Variant chr9-22006274-G-T is described in ClinVar as Benign. ClinVar VariationId is 1279271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0936 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004936.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CDKN2B	NM_004936.4	MANE Select	c.157-27C>A	intron	N/A	NP_004927.2
CDKN2B-AS1	NR_003529.4	MANE Select	n.371+11113G>T	intron	N/A
CDKN2B	NM_078487.2		c.*43-27C>A	intron	N/A	NP_511042.1	P42772-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CDKN2B	ENST00000276925.7	TSL:1 MANE Select	c.157-27C>A	intron	N/A	ENSP00000276925.6	P42772-1
CDKN2B	ENST00000380142.5	TSL:1	c.*43-27C>A	intron	N/A	ENSP00000369487.4	P42772-2
CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.371+11113G>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0866

AC:

13187

AN:

152238

Hom.:

571

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0957

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.0742

Gnomad ASJ

AF:

0.0959

Gnomad EAS

AF:

0.0188

Gnomad SAS

AF:

0.0461

Gnomad FIN

AF:

0.0815

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.0929

Gnomad OTH

AF:

0.0879

GnomAD2 exomes

AF:

0.0745

AC:

16944

AN:

227284

AF XY:

0.0758

show subpopulations

Gnomad AFR exome

AF:

0.0941

Gnomad AMR exome

AF:

0.0483

Gnomad ASJ exome

AF:

0.0981

Gnomad EAS exome

AF:

0.0208

Gnomad FIN exome

AF:

0.0791

Gnomad NFE exome

AF:

0.0926

Gnomad OTH exome

AF:

0.0801

GnomAD4 exome

AF:

0.0852

AC:

123324

AN:

1448132

Hom.:

5450

Cov.:

AF XY:

0.0848

AC XY:

61154

AN XY:

720918

show subpopulations

African (AFR)

AF:

0.0973

AC:

3256

AN:

33454

American (AMR)

AF:

0.0512

AC:

2287

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.0941

AC:

2457

AN:

26118

East Asian (EAS)

AF:

0.0175

AC:

695

AN:

39682

South Asian (SAS)

AF:

0.0561

AC:

4835

AN:

86220

European-Finnish (FIN)

AF:

0.0763

AC:

3086

AN:

40440

Middle Eastern (MID)

AF:

0.0897

AC:

509

AN:

5674

European-Non Finnish (NFE)

AF:

0.0908

AC:

100945

AN:

1111606

Other (OTH)

AF:

0.0872

AC:

5254

AN:

60244

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

6635

13270

19905

26540

33175

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3634

7268

10902

14536

18170

<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:

0.0867

AC:

13209

AN:

152356

Hom.:

573

Cov.:

AF XY:

0.0854

AC XY:

6364

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.0960

AC:

3993

AN:

41574

American (AMR)

AF:

0.0741

AC:

1135

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.0959

AC:

333

AN:

3472

East Asian (EAS)

AF:

0.0193

AC:

100

AN:

5190

South Asian (SAS)

AF:

0.0464

AC:

224

AN:

4832

European-Finnish (FIN)

AF:

0.0815

AC:

865

AN:

10620

Middle Eastern (MID)

AF:

0.133

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0928

AC:

6316

AN:

68034

Other (OTH)

AF:

0.0870

AC:

184

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

620

1240

1861

2481

3101

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

150

300

450

600

750

<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:

0.0884

Hom.:

354

Bravo

AF:

0.0850

Asia WGS

AF:

0.0440

AC:

153

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.1

(source)

DANN

Benign

0.83

PhyloP100

-0.056

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over