Genetic Variant CDKN2B-AS1:n.847-4873T>C (chr9-22041444-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.847-4873T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.59 in 151,906 control chromosomes in the GnomAD database, including 27,584 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 ( 27584 hom., cov: 32)

Consequence

CDKN2B-AS1
ENST00000428597.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.14

Publications

21 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 (AFR) allele frequency at 95% confidence interval = 0.729 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.847-4873T>C	intron	N/A
CDKN2B-AS1	NR_047532.2		n.534-4873T>C	intron	N/A
CDKN2B-AS1	NR_047533.2		n.372-5307T>C	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.847-4873T>C	intron	N/A
CDKN2B-AS1	ENST00000455933.8	TSL:1	n.341-5307T>C	intron	N/A
CDKN2B-AS1	ENST00000577551.5	TSL:1	n.261-5307T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.590

AC:

89485

AN:

151788

Hom.:

27550

Cov.:

show subpopulations

Gnomad AFR

AF:

0.735

Gnomad AMI

AF:

0.502

Gnomad AMR

AF:

0.692

Gnomad ASJ

AF:

0.614

Gnomad EAS

AF:

0.694

Gnomad SAS

AF:

0.646

Gnomad FIN

AF:

0.495

Gnomad MID

AF:

0.662

Gnomad NFE

AF:

0.479

Gnomad OTH

AF:

0.619

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

GnomAD4 genome

AF:

0.590

AC:

89571

AN:

151906

Hom.:

27584

Cov.:

AF XY:

0.592

AC XY:

43939

AN XY:

74242

show subpopulations

African (AFR)

AF:

0.735

AC:

30486

AN:

41450

American (AMR)

AF:

0.692

AC:

10559

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.614

AC:

2129

AN:

3468

East Asian (EAS)

AF:

0.694

AC:

3572

AN:

5150

South Asian (SAS)

AF:

0.646

AC:

3112

AN:

4820

European-Finnish (FIN)

AF:

0.495

AC:

5227

AN:

10558

Middle Eastern (MID)

AF:

0.668

AC:

195

AN:

292

European-Non Finnish (NFE)

AF:

0.479

AC:

32542

AN:

67902

Other (OTH)

AF:

0.613

AC:

1292

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1765

3530

5294

7059

8824

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

742

1484

2226

2968

3710

<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:

0.513

Hom.:

12037

Bravo

AF:

0.612

Asia WGS

AF:

0.669

AC:

2326

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.36

(source)

DANN

Benign

0.80

PhyloP100

-1.1

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