Genetic Variant CDKN2B-AS1:n.2774+205T>C (chr9-22112600-T-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.2774+205T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 152,040 control chromosomes in the GnomAD database, including 26,943 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 0.59 ( 26943 hom., cov: 32)

Consequence

CDKN2B-AS1
ENST00000428597.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0490

Publications

26 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=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.724 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.2774+205T>C	intron	N/A
CDKN2B-AS1	NR_047532.2		n.1563+205T>C	intron	N/A
CDKN2B-AS1	NR_047534.2		n.827+205T>C	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.2774+205T>C	intron	N/A
CDKN2B-AS1	ENST00000577551.5	TSL:1	n.609+205T>C	intron	N/A
CDKN2B-AS1	ENST00000580576.6	TSL:1	n.1563+205T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.587

AC:

89195

AN:

151922

Hom.:

26920

Cov.:

show subpopulations

Gnomad AFR

AF:

0.730

Gnomad AMI

AF:

0.497

Gnomad AMR

AF:

0.578

Gnomad ASJ

AF:

0.652

Gnomad EAS

AF:

0.670

Gnomad SAS

AF:

0.601

Gnomad FIN

AF:

0.427

Gnomad MID

AF:

0.703

Gnomad NFE

AF:

0.516

Gnomad OTH

AF:

0.610

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

GnomAD4 genome

AF:

0.587

AC:

89275

AN:

152040

Hom.:

26943

Cov.:

AF XY:

0.580

AC XY:

43081

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.731

AC:

30311

AN:

41488

American (AMR)

AF:

0.578

AC:

8833

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.652

AC:

2261

AN:

3468

East Asian (EAS)

AF:

0.670

AC:

3459

AN:

5164

South Asian (SAS)

AF:

0.600

AC:

2886

AN:

4810

European-Finnish (FIN)

AF:

0.427

AC:

4507

AN:

10556

Middle Eastern (MID)

AF:

0.694

AC:

204

AN:

294

European-Non Finnish (NFE)

AF:

0.516

AC:

35081

AN:

67954

Other (OTH)

AF:

0.607

AC:

1281

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1847

3695

5542

7390

9237

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

756

1512

2268

3024

3780

<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:

0.560

Hom.:

17331

Bravo

AF:

0.603

Asia WGS

AF:

0.616

AC:

2142

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

2.8

(source)

DANN

Benign

0.77

PhyloP100

0.049

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