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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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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
CDKN2B-AS1	NR_003529.4 link	n.371+2979T>G	intron_variant	Intron 1 of 18
CDKN2B-AS1	NR_047532.2 link	n.371+2979T>G	intron_variant	Intron 1 of 13
CDKN2B-AS1	NR_047533.2 link	n.371+2979T>G	intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
CDKN2B-AS1	ENST00000428597.7 link	n.371+2979T>G	intron_variant	Intron 1 of 18	1
CDKN2B-AS1	ENST00000455933.8 link	n.340+2979T>G	intron_variant	Intron 1 of 4	1
CDKN2B-AS1	ENST00000577551.5 link	n.260+2979T>G	intron_variant	Intron 1 of 6	1

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 v4.3

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over