dbSNP rs518394: CDKN2B-AS1:n.372-9759G>C (chr9-22019674-G-C) – 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.372-9759G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 152,002 control chromosomes in the GnomAD database, including 8,575 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 0.30 ( 8575 hom., cov: 31)

Consequence

CDKN2B-AS1
ENST00000428597.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.07

Publications

42 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=-0.91).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.433 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.372-9759G>C	intron	N/A
CDKN2B-AS1	NR_047532.2		n.372-9759G>C	intron	N/A
CDKN2B-AS1	NR_047533.2		n.371+24513G>C	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.372-9759G>C	intron	N/A
CDKN2B-AS1	ENST00000455933.8	TSL:1	n.340+24513G>C	intron	N/A
CDKN2B-AS1	ENST00000577551.5	TSL:1	n.260+24513G>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.295

AC:

44881

AN:

151884

Hom.:

8568

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0762

Gnomad AMI

AF:

0.503

Gnomad AMR

AF:

0.226

Gnomad ASJ

AF:

0.324

Gnomad EAS

AF:

0.108

Gnomad SAS

AF:

0.265

Gnomad FIN

AF:

0.432

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.437

Gnomad OTH

AF:

0.281

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

GnomAD4 genome

AF:

0.295

AC:

44889

AN:

152002

Hom.:

8575

Cov.:

AF XY:

0.293

AC XY:

21800

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.0761

AC:

3156

AN:

41496

American (AMR)

AF:

0.226

AC:

3445

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.324

AC:

1123

AN:

3466

East Asian (EAS)

AF:

0.108

AC:

557

AN:

5168

South Asian (SAS)

AF:

0.264

AC:

1271

AN:

4808

European-Finnish (FIN)

AF:

0.432

AC:

4549

AN:

10530

Middle Eastern (MID)

AF:

0.177

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.437

AC:

29676

AN:

67952

Other (OTH)

AF:

0.286

AC:

604

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1406

2812

4218

5624

7030

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

454

908

1362

1816

2270

<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:

0.376

Hom.:

1704

Bravo

AF:

0.272

Asia WGS

AF:

0.210

AC:

733

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

6.7

(source)

DANN

Benign

0.68

PhyloP100

1.1

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