Genetic Variant CDKN2B-AS1:n.847-2390A>G (chr9-22043927-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.847-2390A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 151,872 control chromosomes in the GnomAD database, including 7,702 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 0.28 ( 7702 hom., cov: 32)

Consequence

CDKN2B-AS1
ENST00000428597.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.908

Publications

117 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=-0.95).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.41 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.847-2390A>G	intron	N/A
CDKN2B-AS1	NR_047532.2		n.534-2390A>G	intron	N/A
CDKN2B-AS1	NR_047533.2		n.372-2824A>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.847-2390A>G	intron	N/A
CDKN2B-AS1	ENST00000455933.8	TSL:1	n.341-2824A>G	intron	N/A
CDKN2B-AS1	ENST00000577551.5	TSL:1	n.261-2824A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.280

AC:

42429

AN:

151754

Hom.:

7696

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0723

Gnomad AMI

AF:

0.449

Gnomad AMR

AF:

0.213

Gnomad ASJ

AF:

0.279

Gnomad EAS

AF:

0.109

Gnomad SAS

AF:

0.242

Gnomad FIN

AF:

0.418

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.414

Gnomad OTH

AF:

0.260

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

GnomAD4 genome

AF:

0.279

AC:

42435

AN:

151872

Hom.:

7702

Cov.:

AF XY:

0.279

AC XY:

20675

AN XY:

74206

show subpopulations

African (AFR)

AF:

0.0721

AC:

2993

AN:

41512

American (AMR)

AF:

0.213

AC:

3248

AN:

15230

Ashkenazi Jewish (ASJ)

AF:

0.279

AC:

968

AN:

3464

East Asian (EAS)

AF:

0.109

AC:

562

AN:

5166

South Asian (SAS)

AF:

0.241

AC:

1164

AN:

4826

European-Finnish (FIN)

AF:

0.418

AC:

4409

AN:

10544

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.414

AC:

28077

AN:

67820

Other (OTH)

AF:

0.265

AC:

559

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1393

2786

4178

5571

6964

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

432

864

1296

1728

2160

<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:

0.370

Hom.:

44502

Bravo

AF:

0.256

Asia WGS

AF:

0.204

AC:

711

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.32

(source)

DANN

Benign

0.55

PhyloP100

-0.91

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