dbSNP rs1537378: CDKN2B-AS1:n.2085-338A>G (chr9-22061615-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 ENST00000428597.7(CDKN2B-AS1):n.2085-338A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.735 in 152,034 control chromosomes in the GnomAD database, including 42,619 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 0.73 ( 42619 hom., cov: 32)

Consequence

CDKN2B-AS1
ENST00000428597.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.282

Publications

45 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 ENST00000428597.7, 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=-1.0).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.924 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000428597.7. 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.2085-338A>G	intron	N/A
CDKN2B-AS1	NR_047532.2		n.1075+5228A>G	intron	N/A
CDKN2B-AS1	NR_047533.2		n.644+12387A>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.2085-338A>G	intron	N/A
CDKN2B-AS1	ENST00000455933.8	TSL:1	n.749+5228A>G	intron	N/A
CDKN2B-AS1	ENST00000577551.5	TSL:1	n.533+12387A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.735

AC:

111622

AN:

151916

Hom.:

42560

Cov.:

show subpopulations

Gnomad AFR

AF:

0.931

Gnomad AMI

AF:

0.558

Gnomad AMR

AF:

0.796

Gnomad ASJ

AF:

0.754

Gnomad EAS

AF:

0.871

Gnomad SAS

AF:

0.766

Gnomad FIN

AF:

0.622

Gnomad MID

AF:

0.829

Gnomad NFE

AF:

0.607

Gnomad OTH

AF:

0.749

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

GnomAD4 genome

AF:

0.735

AC:

111734

AN:

152034

Hom.:

42619

Cov.:

AF XY:

0.735

AC XY:

54592

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.931

AC:

38678

AN:

41526

American (AMR)

AF:

0.796

AC:

12160

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.754

AC:

2615

AN:

3470

East Asian (EAS)

AF:

0.871

AC:

4505

AN:

5170

South Asian (SAS)

AF:

0.766

AC:

3678

AN:

4802

European-Finnish (FIN)

AF:

0.622

AC:

6545

AN:

10530

Middle Eastern (MID)

AF:

0.830

AC:

244

AN:

294

European-Non Finnish (NFE)

AF:

0.607

AC:

41233

AN:

67946

Other (OTH)

AF:

0.743

AC:

1568

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1347

2694

4040

5387

6734

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

832

1664

2496

3328

4160

<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:

0.646

Hom.:

53551

Bravo

AF:

0.756

Asia WGS

AF:

0.786

AC:

2706

AN:

3444

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.87

(source)

DANN

Benign

0.68

PhyloP100

-0.28

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