Genetic Variant CDKN2B-AS1:n.1253-2564A>G (chr9-22053688-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.1253-2564A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 152,066 control chromosomes in the GnomAD database, including 26,901 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 0.58 ( 26901 hom., cov: 32)

Consequence

CDKN2B-AS1
ENST00000428597.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.189

Publications

24 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=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.697 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.1253-2564A>G	intron	N/A
CDKN2B-AS1	NR_047532.2		n.940-2564A>G	intron	N/A
CDKN2B-AS1	NR_047533.2		n.644+4460A>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.1253-2564A>G	intron	N/A
CDKN2B-AS1	ENST00000455933.8	TSL:1	n.614-2564A>G	intron	N/A
CDKN2B-AS1	ENST00000577551.5	TSL:1	n.533+4460A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.584

AC:

88796

AN:

151948

Hom.:

26870

Cov.:

show subpopulations

Gnomad AFR

AF:

0.704

Gnomad AMI

AF:

0.504

Gnomad AMR

AF:

0.694

Gnomad ASJ

AF:

0.613

Gnomad EAS

AF:

0.695

Gnomad SAS

AF:

0.642

Gnomad FIN

AF:

0.503

Gnomad MID

AF:

0.665

Gnomad NFE

AF:

0.485

Gnomad OTH

AF:

0.616

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

GnomAD4 genome

AF:

0.584

AC:

88878

AN:

152066

Hom.:

26901

Cov.:

AF XY:

0.586

AC XY:

43579

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.704

AC:

29191

AN:

41464

American (AMR)

AF:

0.695

AC:

10614

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.613

AC:

2126

AN:

3470

East Asian (EAS)

AF:

0.694

AC:

3587

AN:

5166

South Asian (SAS)

AF:

0.641

AC:

3094

AN:

4824

European-Finnish (FIN)

AF:

0.503

AC:

5313

AN:

10564

Middle Eastern (MID)

AF:

0.667

AC:

196

AN:

294

European-Non Finnish (NFE)

AF:

0.486

AC:

33008

AN:

67984

Other (OTH)

AF:

0.611

AC:

1290

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1853

3706

5560

7413

9266

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

746

1492

2238

2984

3730

<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:

0.567

Hom.:

16151

Bravo

AF:

0.605

Asia WGS

AF:

0.666

AC:

2314

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.8

(source)

DANN

Benign

0.72

PhyloP100

0.19

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