dbSNP rs1333037: CDKN2B-AS1:n.847-5551C>T (chr9-22040766-C-T) – 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.847-5551C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.715 in 151,902 control chromosomes in the GnomAD database, including 40,750 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 0.72 ( 40750 hom., cov: 32)

Consequence

CDKN2B-AS1
ENST00000428597.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.53

Publications

31 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=-0.94).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.919 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.847-5551C>T	intron	N/A
CDKN2B-AS1	NR_047532.2		n.534-5551C>T	intron	N/A
CDKN2B-AS1	NR_047533.2		n.372-5985C>T	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.847-5551C>T	intron	N/A
CDKN2B-AS1	ENST00000455933.8	TSL:1	n.341-5985C>T	intron	N/A
CDKN2B-AS1	ENST00000577551.5	TSL:1	n.261-5985C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.715

AC:

108570

AN:

151784

Hom.:

40691

Cov.:

show subpopulations

Gnomad AFR

AF:

0.926

Gnomad AMI

AF:

0.530

Gnomad AMR

AF:

0.783

Gnomad ASJ

AF:

0.720

Gnomad EAS

AF:

0.890

Gnomad SAS

AF:

0.754

Gnomad FIN

AF:

0.579

Gnomad MID

AF:

0.832

Gnomad NFE

AF:

0.578

Gnomad OTH

AF:

0.734

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

GnomAD4 genome

AF:

0.715

AC:

108682

AN:

151902

Hom.:

40750

Cov.:

AF XY:

0.716

AC XY:

53179

AN XY:

74228

show subpopulations

African (AFR)

AF:

0.927

AC:

38446

AN:

41492

American (AMR)

AF:

0.783

AC:

11945

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.720

AC:

2498

AN:

3468

East Asian (EAS)

AF:

0.890

AC:

4575

AN:

5140

South Asian (SAS)

AF:

0.754

AC:

3633

AN:

4816

European-Finnish (FIN)

AF:

0.579

AC:

6095

AN:

10534

Middle Eastern (MID)

AF:

0.833

AC:

245

AN:

294

European-Non Finnish (NFE)

AF:

0.578

AC:

39222

AN:

67890

Other (OTH)

AF:

0.729

AC:

1542

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1422

2845

4267

5690

7112

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

816

1632

2448

3264

4080

<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:

0.626

Hom.:

52039

Bravo

AF:

0.739

Asia WGS

AF:

0.796

AC:

2767

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.0040

(source)

DANN

Benign

0.40

PhyloP100

-4.5

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