dbSNP rs495490: CDKN2B-AS1:n.371+15252A>G (chr9-22010413-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.371+15252A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0671 in 152,286 control chromosomes in the GnomAD database, including 463 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 0.067 ( 463 hom., cov: 33)

Consequence

CDKN2B-AS1
ENST00000428597.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.130

Publications

15 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:

ENSG00000264545 (HGNC:):

ENSG00000264545 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=-0.88).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0987 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.371+15252A>G	intron	N/A
CDKN2B-AS1	NR_047532.2		n.371+15252A>G	intron	N/A
CDKN2B-AS1	NR_047533.2		n.371+15252A>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.371+15252A>G	intron	N/A
CDKN2B-AS1	ENST00000455933.8	TSL:1	n.340+15252A>G	intron	N/A
CDKN2B-AS1	ENST00000577551.5	TSL:1	n.260+15252A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0671

AC:

10209

AN:

152168

Hom.:

462

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0181

Gnomad AMI

AF:

0.273

Gnomad AMR

AF:

0.0581

Gnomad ASJ

AF:

0.0933

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0323

Gnomad FIN

AF:

0.0762

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.101

Gnomad OTH

AF:

0.0789

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

GnomAD4 genome

AF:

0.0671

AC:

10212

AN:

152286

Hom.:

463

Cov.:

AF XY:

0.0653

AC XY:

4859

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.0181

AC:

751

AN:

41558

American (AMR)

AF:

0.0580

AC:

888

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0933

AC:

324

AN:

3472

East Asian (EAS)

AF:

0.000579

AC:

AN:

5184

South Asian (SAS)

AF:

0.0325

AC:

157

AN:

4828

European-Finnish (FIN)

AF:

0.0762

AC:

808

AN:

10604

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.101

AC:

6847

AN:

68022

Other (OTH)

AF:

0.0799

AC:

169

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

507

1014

1520

2027

2534

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

232

348

464

580

<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:

0.0885

Hom.:

323

Bravo

AF:

0.0648

Asia WGS

AF:

0.0350

AC:

121

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

5.1

(source)

DANN

Benign

0.70

PhyloP100

-0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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