Genetic Variant CDKN2B-AS1:n.2908+2161A>G (chr9-22115960-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000422420.3(CDKN2B-AS1):n.299+2161A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 152,034 control chromosomes in the GnomAD database, including 33,471 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 0.64 ( 33471 hom., cov: 31)

Consequence

CDKN2B-AS1
ENST00000422420.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.28

Publications

238 publications found

Variant links:

COSMIC-nc: COSV69592447

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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new If you want to explore the variant's impact on the transcript ENST00000422420.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-1.01).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000422420.3. 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.2908+2161A>G	intron	N/A
CDKN2B-AS1	NR_047532.2		n.1697+2161A>G	intron	N/A
CDKN2B-AS1	NR_047534.2		n.961+2161A>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.2908+2161A>G	intron	N/A
CDKN2B-AS1	ENST00000422420.3	TSL:1	n.299+2161A>G	intron	N/A
CDKN2B-AS1	ENST00000577551.5	TSL:1	n.610-2684A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.642

AC:

97507

AN:

151916

Hom.:

33427

Cov.:

show subpopulations

Gnomad AFR

AF:

0.898

Gnomad AMI

AF:

0.496

Gnomad AMR

AF:

0.611

Gnomad ASJ

AF:

0.676

Gnomad EAS

AF:

0.670

Gnomad SAS

AF:

0.625

Gnomad FIN

AF:

0.432

Gnomad MID

AF:

0.756

Gnomad NFE

AF:

0.524

Gnomad OTH

AF:

0.664

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

GnomAD4 genome

AF:

0.642

AC:

97608

AN:

152034

Hom.:

33471

Cov.:

AF XY:

0.634

AC XY:

47094

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.898

AC:

37268

AN:

41508

American (AMR)

AF:

0.611

AC:

9331

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.676

AC:

2345

AN:

3468

East Asian (EAS)

AF:

0.670

AC:

3461

AN:

5162

South Asian (SAS)

AF:

0.623

AC:

3005

AN:

4820

European-Finnish (FIN)

AF:

0.432

AC:

4549

AN:

10542

Middle Eastern (MID)

AF:

0.752

AC:

221

AN:

294

European-Non Finnish (NFE)

AF:

0.524

AC:

35585

AN:

67956

Other (OTH)

AF:

0.659

AC:

1392

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1585

3171

4756

6342

7927

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

774

1548

2322

3096

3870

<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:

0.558

Hom.:

112621

Bravo

AF:

0.664

Asia WGS

AF:

0.639

AC:

2220

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.072

(source)

DANN

Benign

0.22

PhyloP100

-2.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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