dbSNP rs2151280: CDKN2B-AS1:n.846+1734G>A (chr9-22034720-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000652420.1(CDKN2B-AS1):n.2395G>A 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 0.465 in 151,790 control chromosomes in the GnomAD database, including 17,533 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 0.46 ( 17533 hom., cov: 32)

Consequence

CDKN2B-AS1
ENST00000652420.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0860

Publications

87 publications found

Variant links:

COSMIC-nc: COSV68676812

Genes affected

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:

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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=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000652420.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CDKN2B-AS1	NR_003529.4	MANE Select	n.846+1734G>A	intron	N/A
CDKN2B-AS1	NR_047532.2		n.533+5126G>A	intron	N/A
CDKN2B-AS1	NR_047533.2		n.372-12031G>A	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.846+1734G>A	intron	N/A
CDKN2B-AS1	ENST00000455933.8	TSL:1	n.341-12031G>A	intron	N/A
CDKN2B-AS1	ENST00000577551.5	TSL:1	n.261-12031G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.465

AC:

70565

AN:

151672

Hom.:

17538

Cov.:

show subpopulations

Gnomad AFR

AF:

0.315

Gnomad AMI

AF:

0.503

Gnomad AMR

AF:

0.641

Gnomad ASJ

AF:

0.601

Gnomad EAS

AF:

0.674

Gnomad SAS

AF:

0.632

Gnomad FIN

AF:

0.501

Gnomad MID

AF:

0.641

Gnomad NFE

AF:

0.474

Gnomad OTH

AF:

0.519

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.465

AC:

70576

AN:

151790

Hom.:

17533

Cov.:

AF XY:

0.472

AC XY:

35019

AN XY:

74188

show subpopulations

African (AFR)

AF:

0.315

AC:

13020

AN:

41384

American (AMR)

AF:

0.641

AC:

9778

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.601

AC:

2082

AN:

3464

East Asian (EAS)

AF:

0.673

AC:

3465

AN:

5146

South Asian (SAS)

AF:

0.632

AC:

3046

AN:

4820

European-Finnish (FIN)

AF:

0.501

AC:

5266

AN:

10518

Middle Eastern (MID)

AF:

0.645

AC:

187

AN:

290

European-Non Finnish (NFE)

AF:

0.474

AC:

32186

AN:

67900

Other (OTH)

AF:

0.515

AC:

1087

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1852

3705

5557

7410

9262

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

644

1288

1932

2576

3220

<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:

0.467

Hom.:

35907

Bravo

AF:

0.468

Asia WGS

AF:

0.620

AC:

2154

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.1

(source)

DANN

Benign

0.71

PhyloP100

-0.086

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over