Genetic Variant CDKN2B-AS1:n.2449-12061C>T (chr9-22084311-C-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.2449-12061C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 152,012 control chromosomes in the GnomAD database, including 24,168 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 0.56 ( 24168 hom., cov: 32)

Consequence

CDKN2B-AS1
ENST00000428597.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.338

Publications

49 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 (EAS) allele frequency at 95% confidence interval = 0.676 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.2449-12061C>T	intron	N/A
CDKN2B-AS1	NR_047532.2		n.1076-7997C>T	intron	N/A
CDKN2B-AS1	NR_047534.2		n.645-12947C>T	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.2449-12061C>T	intron	N/A
CDKN2B-AS1	ENST00000577551.5	TSL:1	n.534-28009C>T	intron	N/A
CDKN2B-AS1	ENST00000580576.6	TSL:1	n.1076-7997C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.556

AC:

84445

AN:

151890

Hom.:

24151

Cov.:

show subpopulations

Gnomad AFR

AF:

0.681

Gnomad AMI

AF:

0.446

Gnomad AMR

AF:

0.523

Gnomad ASJ

AF:

0.635

Gnomad EAS

AF:

0.695

Gnomad SAS

AF:

0.611

Gnomad FIN

AF:

0.413

Gnomad MID

AF:

0.712

Gnomad NFE

AF:

0.490

Gnomad OTH

AF:

0.587

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

GnomAD4 genome

AF:

0.556

AC:

84516

AN:

152012

Hom.:

24168

Cov.:

AF XY:

0.551

AC XY:

40880

AN XY:

74256

show subpopulations

African (AFR)

AF:

0.681

AC:

28266

AN:

41478

American (AMR)

AF:

0.523

AC:

7992

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.635

AC:

2203

AN:

3472

East Asian (EAS)

AF:

0.695

AC:

3592

AN:

5168

South Asian (SAS)

AF:

0.610

AC:

2940

AN:

4820

European-Finnish (FIN)

AF:

0.413

AC:

4343

AN:

10526

Middle Eastern (MID)

AF:

0.707

AC:

208

AN:

294

European-Non Finnish (NFE)

AF:

0.490

AC:

33338

AN:

67970

Other (OTH)

AF:

0.584

AC:

1228

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1869

3737

5606

7474

9343

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

734

1468

2202

2936

3670

<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:

0.514

Hom.:

61403

Bravo

AF:

0.566

Asia WGS

AF:

0.626

AC:

2177

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

6.8

(source)

DANN

Benign

0.60

PhyloP100

0.34

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