dbSNP rs10965235: CDKN2B-AS1:n.2908+1307C>A (chr9-22115106-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000422420.3(CDKN2B-AS1):n.299+1307C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,084 control chromosomes in the GnomAD database, including 4,797 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 0.15 ( 4797 hom., cov: 32)

Consequence

CDKN2B-AS1
ENST00000422420.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.896

Publications

57 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 ENST00000422420.3, 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=-0.98).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000422420.3. 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.2908+1307C>A	intron	N/A
CDKN2B-AS1	NR_047532.2		n.1697+1307C>A	intron	N/A
CDKN2B-AS1	NR_047534.2		n.961+1307C>A	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.2908+1307C>A	intron	N/A
CDKN2B-AS1	ENST00000422420.3	TSL:1	n.299+1307C>A	intron	N/A
CDKN2B-AS1	ENST00000577551.5	TSL:1	n.609+2711C>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.146

AC:

22126

AN:

151966

Hom.:

4776

Cov.:

show subpopulations

Gnomad AFR

AF:

0.471

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0582

Gnomad ASJ

AF:

0.0133

Gnomad EAS

AF:

0.180

Gnomad SAS

AF:

0.0693

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.00328

Gnomad OTH

AF:

0.105

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

GnomAD4 genome

AF:

0.146

AC:

22200

AN:

152084

Hom.:

4797

Cov.:

AF XY:

0.142

AC XY:

10588

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.472

AC:

19535

AN:

41412

American (AMR)

AF:

0.0582

AC:

889

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0133

AC:

AN:

3468

East Asian (EAS)

AF:

0.180

AC:

934

AN:

5176

South Asian (SAS)

AF:

0.0693

AC:

334

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00328

AC:

223

AN:

68014

Other (OTH)

AF:

0.106

AC:

224

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

638

1277

1915

2554

3192

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

190

380

570

760

950

<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:

0.0491

Hom.:

6151

Bravo

AF:

0.166

Asia WGS

AF:

0.117

AC:

404

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.19

(source)

DANN

Benign

0.53

PhyloP100

-0.90

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