Genetic Variant CDKN2B-AS1:n.2698+5820G>T (chr9-22103184-G-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.2698+5820G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 133,078 control chromosomes in the GnomAD database, including 10,868 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 0.39 ( 10868 hom., cov: 25)

Consequence

CDKN2B-AS1
ENST00000428597.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.865

Publications

38 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 (SAS) allele frequency at 95% confidence interval = 0.53 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.2698+5820G>T	intron	N/A
CDKN2B-AS1	NR_047532.2		n.1487+5820G>T	intron	N/A
CDKN2B-AS1	NR_047534.2		n.751+5820G>T	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.2698+5820G>T	intron	N/A
CDKN2B-AS1	ENST00000577551.5	TSL:1	n.534-9136G>T	intron	N/A
CDKN2B-AS1	ENST00000580576.6	TSL:1	n.1487+5820G>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.394

AC:

52339

AN:

132978

Hom.:

10878

Cov.:

show subpopulations

Gnomad AFR

AF:

0.144

Gnomad AMI

AF:

0.501

Gnomad AMR

AF:

0.455

Gnomad ASJ

AF:

0.634

Gnomad EAS

AF:

0.525

Gnomad SAS

AF:

0.549

Gnomad FIN

AF:

0.415

Gnomad MID

AF:

0.634

Gnomad NFE

AF:

0.480

Gnomad OTH

AF:

0.483

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

GnomAD4 genome

AF:

0.393

AC:

52334

AN:

133078

Hom.:

10868

Cov.:

AF XY:

0.391

AC XY:

25171

AN XY:

64402

show subpopulations

African (AFR)

AF:

0.144

AC:

5001

AN:

34792

American (AMR)

AF:

0.455

AC:

5988

AN:

13150

Ashkenazi Jewish (ASJ)

AF:

0.634

AC:

2021

AN:

3190

East Asian (EAS)

AF:

0.525

AC:

2392

AN:

4554

South Asian (SAS)

AF:

0.549

AC:

2328

AN:

4244

European-Finnish (FIN)

AF:

0.415

AC:

3685

AN:

8872

Middle Eastern (MID)

AF:

0.634

AC:

170

AN:

268

European-Non Finnish (NFE)

AF:

0.480

AC:

29472

AN:

61384

Other (OTH)

AF:

0.480

AC:

874

AN:

1820

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

1446

2892

4337

5783

7229

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

528

1056

1584

2112

2640

<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:

0.316

Hom.:

1674

Bravo

AF:

0.340

Asia WGS

AF:

0.449

AC:

1536

AN:

3424

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.24

(source)

DANN

Benign

0.62

PhyloP100

-0.86

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