dbSNP rs3218018: CDKN2B-AS1:n.371+2979T>G (chr9-21998140-T-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+2979T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.087 in 152,304 control chromosomes in the GnomAD database, including 577 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 0.087 ( 577 hom., cov: 33)

Consequence

CDKN2B-AS1
ENST00000428597.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.861

Publications

19 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=-0.78).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.094 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+2979T>G	intron	N/A
CDKN2B-AS1	NR_047532.2		n.371+2979T>G	intron	N/A
CDKN2B-AS1	NR_047533.2		n.371+2979T>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.371+2979T>G	intron	N/A
CDKN2B-AS1	ENST00000455933.8	TSL:1	n.340+2979T>G	intron	N/A
CDKN2B-AS1	ENST00000577551.5	TSL:1	n.260+2979T>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0869

AC:

13221

AN:

152186

Hom.:

575

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0962

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.0751

Gnomad ASJ

AF:

0.0957

Gnomad EAS

AF:

0.0196

Gnomad SAS

AF:

0.0449

Gnomad FIN

AF:

0.0813

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.0930

Gnomad OTH

AF:

0.0880

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

GnomAD4 genome

AF:

0.0870

AC:

13243

AN:

152304

Hom.:

577

Cov.:

AF XY:

0.0855

AC XY:

6364

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.0965

AC:

4013

AN:

41568

American (AMR)

AF:

0.0750

AC:

1147

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0957

AC:

332

AN:

3470

East Asian (EAS)

AF:

0.0200

AC:

104

AN:

5190

South Asian (SAS)

AF:

0.0452

AC:

218

AN:

4828

European-Finnish (FIN)

AF:

0.0813

AC:

863

AN:

10614

Middle Eastern (MID)

AF:

0.133

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0930

AC:

6323

AN:

68016

Other (OTH)

AF:

0.0871

AC:

184

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

619

1238

1856

2475

3094

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

150

300

450

600

750

<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:

0.0912

Hom.:

490

Bravo

AF:

0.0854

Asia WGS

AF:

0.0440

AC:

153

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

(source)

DANN

Benign

0.71

PhyloP100

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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