Genetic Variant CDKN2B-AS1:n.2449-316A>G (chr9-22096056-A-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.2449-316A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 151,878 control chromosomes in the GnomAD database, including 14,245 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

Frequency

Genomes: 𝑓 0.41 ( 14245 hom., cov: 30)

Consequence

CDKN2B-AS1
ENST00000428597.7 intron

Scores

Clinical Significance

risk factor no assertion criteria provided O:1

Conservation

PhyloP100: 1.29

Publications

276 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=-0.89).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.506 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.2449-316A>G	intron	N/A
CDKN2B-AS1	NR_047532.2		n.1238-316A>G	intron	N/A
CDKN2B-AS1	NR_047534.2		n.645-1202A>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.2449-316A>G	intron	N/A
CDKN2B-AS1	ENST00000577551.5	TSL:1	n.534-16264A>G	intron	N/A
CDKN2B-AS1	ENST00000580576.6	TSL:1	n.1238-316A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.415

AC:

63020

AN:

151760

Hom.:

14255

Cov.:

show subpopulations

Gnomad AFR

AF:

0.217

Gnomad AMI

AF:

0.492

Gnomad AMR

AF:

0.457

Gnomad ASJ

AF:

0.623

Gnomad EAS

AF:

0.484

Gnomad SAS

AF:

0.524

Gnomad FIN

AF:

0.434

Gnomad MID

AF:

0.646

Gnomad NFE

AF:

0.496

Gnomad OTH

AF:

0.482

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

GnomAD4 genome

AF:

0.415

AC:

63029

AN:

151878

Hom.:

14245

Cov.:

AF XY:

0.412

AC XY:

30571

AN XY:

74230

show subpopulations

African (AFR)

AF:

0.217

AC:

9001

AN:

41432

American (AMR)

AF:

0.457

AC:

6969

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.623

AC:

2156

AN:

3462

East Asian (EAS)

AF:

0.484

AC:

2488

AN:

5142

South Asian (SAS)

AF:

0.523

AC:

2517

AN:

4814

European-Finnish (FIN)

AF:

0.434

AC:

4566

AN:

10528

Middle Eastern (MID)

AF:

0.636

AC:

187

AN:

294

European-Non Finnish (NFE)

AF:

0.496

AC:

33691

AN:

67952

Other (OTH)

AF:

0.478

AC:

1005

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1753

3506

5260

7013

8766

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

612

1224

1836

2448

3060

<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:

0.469

Hom.:

71864

Bravo

AF:

0.406

Asia WGS

AF:

0.493

AC:

1714

AN:

3478

ClinVar

ClinVar submissions

Significance:risk factor

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Three Vessel Coronary Disease (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

(source)

DANN

Benign

0.76

PhyloP100

1.3

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