dbSNP rs10965227: CDKN2B-AS1:n.2449-14575A>G (chr9-22081797-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.2449-14575A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,286 control chromosomes in the GnomAD database, including 3,127 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 0.17 ( 3127 hom., cov: 33)

Consequence

CDKN2B-AS1
ENST00000428597.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.55

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=-0.83).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.352 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.2449-14575A>G	intron	N/A
CDKN2B-AS1	NR_047532.2		n.1076-10511A>G	intron	N/A
CDKN2B-AS1	NR_047534.2		n.645-15461A>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.2449-14575A>G	intron	N/A
CDKN2B-AS1	ENST00000577551.5	TSL:1	n.534-30523A>G	intron	N/A
CDKN2B-AS1	ENST00000580576.6	TSL:1	n.1076-10511A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.175

AC:

26573

AN:

152168

Hom.:

3124

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0418

Gnomad AMI

AF:

0.350

Gnomad AMR

AF:

0.360

Gnomad ASJ

AF:

0.161

Gnomad EAS

AF:

0.146

Gnomad SAS

AF:

0.178

Gnomad FIN

AF:

0.225

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.206

Gnomad OTH

AF:

0.184

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

GnomAD4 genome

AF:

0.175

AC:

26585

AN:

152286

Hom.:

3127

Cov.:

AF XY:

0.181

AC XY:

13445

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.0417

AC:

1732

AN:

41582

American (AMR)

AF:

0.360

AC:

5505

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.161

AC:

559

AN:

3468

East Asian (EAS)

AF:

0.146

AC:

756

AN:

5182

South Asian (SAS)

AF:

0.180

AC:

871

AN:

4832

European-Finnish (FIN)

AF:

0.225

AC:

2388

AN:

10600

Middle Eastern (MID)

AF:

0.156

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.206

AC:

14023

AN:

68010

Other (OTH)

AF:

0.183

AC:

386

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1070

2140

3209

4279

5349

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

278

556

834

1112

1390

<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:

0.198

Hom.:

3074

Bravo

AF:

0.184

Asia WGS

AF:

0.155

AC:

539

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

(source)

DANN

Benign

0.60

PhyloP100

1.5

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