dbSNP rs17694555: CDKN2B-AS1:n.1252+2068A>G (chr9-22051296-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.1252+2068A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0585 in 152,190 control chromosomes in the GnomAD database, including 324 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 0.058 ( 324 hom., cov: 32)

Consequence

CDKN2B-AS1
ENST00000428597.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0430

Publications

10 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=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0875 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.1252+2068A>G	intron	N/A
CDKN2B-AS1	NR_047532.2		n.939+2068A>G	intron	N/A
CDKN2B-AS1	NR_047533.2		n.644+2068A>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.1252+2068A>G	intron	N/A
CDKN2B-AS1	ENST00000455933.8	TSL:1	n.613+2068A>G	intron	N/A
CDKN2B-AS1	ENST00000577551.5	TSL:1	n.533+2068A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0586

AC:

8906

AN:

152072

Hom.:

324

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0145

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.0490

Gnomad ASJ

AF:

0.0573

Gnomad EAS

AF:

0.0183

Gnomad SAS

AF:

0.0373

Gnomad FIN

AF:

0.0801

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0894

Gnomad OTH

AF:

0.0511

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

GnomAD4 genome

AF:

0.0585

AC:

8903

AN:

152190

Hom.:

324

Cov.:

AF XY:

0.0582

AC XY:

4329

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.0145

AC:

601

AN:

41552

American (AMR)

AF:

0.0489

AC:

747

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.0573

AC:

199

AN:

3470

East Asian (EAS)

AF:

0.0187

AC:

AN:

5182

South Asian (SAS)

AF:

0.0375

AC:

181

AN:

4822

European-Finnish (FIN)

AF:

0.0801

AC:

848

AN:

10590

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0894

AC:

6078

AN:

67990

Other (OTH)

AF:

0.0506

AC:

107

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

433

867

1300

1734

2167

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

106

212

318

424

530

<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:

0.0836

Hom.:

224

Bravo

AF:

0.0529

Asia WGS

AF:

0.0310

AC:

108

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.3

(source)

DANN

Benign

0.59

PhyloP100

0.043

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