Genetic Variant CDKN2B-AS1:n.2448+5912A>G (chr9-22072265-A-G) – 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.2448+5912A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.614 in 152,054 control chromosomes in the GnomAD database, including 30,566 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 0.61 ( 30566 hom., cov: 32)

Consequence

CDKN2B-AS1
ENST00000428597.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.13

Publications

48 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=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.835 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.2448+5912A>G	intron	N/A
CDKN2B-AS1	NR_047532.2		n.1075+15878A>G	intron	N/A
CDKN2B-AS1	NR_047533.2		n.645-5414A>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.2448+5912A>G	intron	N/A
CDKN2B-AS1	ENST00000455933.8	TSL:1	n.750-5414A>G	intron	N/A
CDKN2B-AS1	ENST00000577551.5	TSL:1	n.533+23037A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.614

AC:

93343

AN:

151936

Hom.:

30530

Cov.:

show subpopulations

Gnomad AFR

AF:

0.842

Gnomad AMI

AF:

0.500

Gnomad AMR

AF:

0.558

Gnomad ASJ

AF:

0.664

Gnomad EAS

AF:

0.792

Gnomad SAS

AF:

0.652

Gnomad FIN

AF:

0.444

Gnomad MID

AF:

0.737

Gnomad NFE

AF:

0.496

Gnomad OTH

AF:

0.634

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

GnomAD4 genome

AF:

0.614

AC:

93436

AN:

152054

Hom.:

30566

Cov.:

AF XY:

0.610

AC XY:

45298

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.842

AC:

34976

AN:

41516

American (AMR)

AF:

0.559

AC:

8536

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.664

AC:

2305

AN:

3470

East Asian (EAS)

AF:

0.792

AC:

4094

AN:

5170

South Asian (SAS)

AF:

0.651

AC:

3126

AN:

4804

European-Finnish (FIN)

AF:

0.444

AC:

4683

AN:

10538

Middle Eastern (MID)

AF:

0.738

AC:

217

AN:

294

European-Non Finnish (NFE)

AF:

0.496

AC:

33713

AN:

67958

Other (OTH)

AF:

0.630

AC:

1332

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1703

3406

5110

6813

8516

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

762

1524

2286

3048

3810

<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:

0.519

Hom.:

24659

Bravo

AF:

0.630

Asia WGS

AF:

0.707

AC:

2457

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

6.4

(source)

DANN

Benign

0.82

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