Genetic Variant CDKN2B-AS1:n.847-2194C>T (chr9-22044123-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.847-2194C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.906 in 152,000 control chromosomes in the GnomAD database, including 62,362 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 0.91 ( 62362 hom., cov: 32)

Consequence

CDKN2B-AS1
ENST00000428597.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.732

Publications

25 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=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.958 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.847-2194C>T	intron	N/A
CDKN2B-AS1	NR_047532.2		n.534-2194C>T	intron	N/A
CDKN2B-AS1	NR_047533.2		n.372-2628C>T	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.847-2194C>T	intron	N/A
CDKN2B-AS1	ENST00000455933.8	TSL:1	n.341-2628C>T	intron	N/A
CDKN2B-AS1	ENST00000577551.5	TSL:1	n.261-2628C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.906

AC:

137568

AN:

151882

Hom.:

62316

Cov.:

show subpopulations

Gnomad AFR

AF:

0.894

Gnomad AMI

AF:

0.953

Gnomad AMR

AF:

0.921

Gnomad ASJ

AF:

0.904

Gnomad EAS

AF:

0.981

Gnomad SAS

AF:

0.952

Gnomad FIN

AF:

0.915

Gnomad MID

AF:

0.848

Gnomad NFE

AF:

0.898

Gnomad OTH

AF:

0.905

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

GnomAD4 genome

AF:

0.906

AC:

137672

AN:

152000

Hom.:

62362

Cov.:

AF XY:

0.907

AC XY:

67421

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.894

AC:

37119

AN:

41504

American (AMR)

AF:

0.921

AC:

14036

AN:

15236

Ashkenazi Jewish (ASJ)

AF:

0.904

AC:

3139

AN:

3472

East Asian (EAS)

AF:

0.981

AC:

5059

AN:

5158

South Asian (SAS)

AF:

0.952

AC:

4591

AN:

4824

European-Finnish (FIN)

AF:

0.915

AC:

9682

AN:

10576

Middle Eastern (MID)

AF:

0.854

AC:

251

AN:

294

European-Non Finnish (NFE)

AF:

0.898

AC:

61016

AN:

67916

Other (OTH)

AF:

0.906

AC:

1910

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

692

1384

2077

2769

3461

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

904

1808

2712

3616

4520

<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:

0.900

Hom.:

114922

Bravo

AF:

0.907

Asia WGS

AF:

0.949

AC:

3296

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.0

(source)

DANN

Benign

0.72

PhyloP100

0.73

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