Genetic Variant CDKN2B-AS1:n.533+845A>G (chr9-22030439-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 ENST00000645313.2(CDKN2B-AS1):n.1346A>G 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 0.899 in 152,162 control chromosomes in the GnomAD database, including 61,442 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 0.90 ( 61441 hom., cov: 31)

Exomes 𝑓: 1.0 ( 1 hom. )

Consequence

CDKN2B-AS1
ENST00000645313.2 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0880

Publications

24 publications found

Variant links:

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 ENST00000645313.2, 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=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000645313.2. 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.533+845A>G	intron	N/A
CDKN2B-AS1	NR_047532.2		n.533+845A>G	intron	N/A
CDKN2B-AS1	NR_047533.2		n.372-16312A>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.533+845A>G	intron	N/A
CDKN2B-AS1	ENST00000455933.8	TSL:1	n.341-16312A>G	intron	N/A
CDKN2B-AS1	ENST00000577551.5	TSL:1	n.261-16312A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.899

AC:

136623

AN:

152042

Hom.:

61402

Cov.:

show subpopulations

Gnomad AFR

AF:

0.869

Gnomad AMI

AF:

0.955

Gnomad AMR

AF:

0.917

Gnomad ASJ

AF:

0.904

Gnomad EAS

AF:

0.981

Gnomad SAS

AF:

0.952

Gnomad FIN

AF:

0.916

Gnomad MID

AF:

0.867

Gnomad NFE

AF:

0.899

Gnomad OTH

AF:

0.903

GnomAD4 exome

AF:

1.00

AC:

AN:

Hom.:

Cov.:

AF XY:

1.00

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

1.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.899

AC:

136719

AN:

152160

Hom.:

61441

Cov.:

AF XY:

0.901

AC XY:

67013

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.869

AC:

36041

AN:

41490

American (AMR)

AF:

0.918

AC:

14030

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.904

AC:

3137

AN:

3470

East Asian (EAS)

AF:

0.980

AC:

5073

AN:

5174

South Asian (SAS)

AF:

0.952

AC:

4592

AN:

4824

European-Finnish (FIN)

AF:

0.916

AC:

9706

AN:

10596

Middle Eastern (MID)

AF:

0.867

AC:

255

AN:

294

European-Non Finnish (NFE)

AF:

0.899

AC:

61107

AN:

68000

Other (OTH)

AF:

0.904

AC:

1909

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

715

1429

2144

2858

3573

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

904

1808

2712

3616

4520

<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:

0.900

Hom.:

44473

Bravo

AF:

0.898

Asia WGS

AF:

0.954

AC:

3315

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.0

(source)

DANN

Benign

0.88

PhyloP100

-0.088

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

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