Genetic Variant CDKN2B-AS1:n.2449-14974G>T (chr9-22081398-G-T) – 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.2449-14974G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 151,772 control chromosomes in the GnomAD database, including 31,377 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 0.62 ( 31377 hom., cov: 29)

Consequence

CDKN2B-AS1
ENST00000428597.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0250

Publications

72 publications found

Variant links:

COSMIC-nc: COSV70107251

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=-0.96).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.882 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.2449-14974G>T	intron	N/A
CDKN2B-AS1	NR_047532.2		n.1076-10910G>T	intron	N/A
CDKN2B-AS1	NR_047534.2		n.645-15860G>T	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.2449-14974G>T	intron	N/A
CDKN2B-AS1	ENST00000577551.5	TSL:1	n.534-30922G>T	intron	N/A
CDKN2B-AS1	ENST00000580576.6	TSL:1	n.1076-10910G>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.617

AC:

93631

AN:

151654

Hom.:

31335

Cov.:

show subpopulations

Gnomad AFR

AF:

0.890

Gnomad AMI

AF:

0.446

Gnomad AMR

AF:

0.553

Gnomad ASJ

AF:

0.645

Gnomad EAS

AF:

0.694

Gnomad SAS

AF:

0.613

Gnomad FIN

AF:

0.413

Gnomad MID

AF:

0.731

Gnomad NFE

AF:

0.492

Gnomad OTH

AF:

0.636

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

GnomAD4 genome

AF:

0.618

AC:

93730

AN:

151772

Hom.:

31377

Cov.:

AF XY:

0.609

AC XY:

45186

AN XY:

74170

show subpopulations

African (AFR)

AF:

0.890

AC:

36876

AN:

41448

American (AMR)

AF:

0.553

AC:

8415

AN:

15228

Ashkenazi Jewish (ASJ)

AF:

0.645

AC:

2239

AN:

3470

East Asian (EAS)

AF:

0.694

AC:

3575

AN:

5150

South Asian (SAS)

AF:

0.612

AC:

2947

AN:

4812

European-Finnish (FIN)

AF:

0.413

AC:

4337

AN:

10510

Middle Eastern (MID)

AF:

0.728

AC:

214

AN:

294

European-Non Finnish (NFE)

AF:

0.492

AC:

33397

AN:

67856

Other (OTH)

AF:

0.632

AC:

1327

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1572

3144

4716

6288

7860

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

758

1516

2274

3032

3790

<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:

0.528

Hom.:

45197

Bravo

AF:

0.637

Asia WGS

AF:

0.647

AC:

2249

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

1.8

(source)

DANN

Benign

0.64

PhyloP100

-0.025

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