dbSNP rs7044859: CDKN2B-AS1:n.372-10651T>A (chr9-22018782-T-A) – 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.372-10651T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 152,128 control chromosomes in the GnomAD database, including 25,124 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 ( 25124 hom., cov: 33)

Consequence

CDKN2B-AS1
ENST00000428597.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.106

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:

ENSG00000264545 (HGNC:):

ENSG00000264545 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=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.691 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.372-10651T>A	intron	N/A
CDKN2B-AS1	NR_047532.2		n.372-10651T>A	intron	N/A
CDKN2B-AS1	NR_047533.2		n.371+23621T>A	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.372-10651T>A	intron	N/A
CDKN2B-AS1	ENST00000455933.8	TSL:1	n.340+23621T>A	intron	N/A
CDKN2B-AS1	ENST00000577551.5	TSL:1	n.260+23621T>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.562

AC:

85437

AN:

152010

Hom.:

25099

Cov.:

show subpopulations

Gnomad AFR

AF:

0.698

Gnomad AMI

AF:

0.446

Gnomad AMR

AF:

0.673

Gnomad ASJ

AF:

0.566

Gnomad EAS

AF:

0.674

Gnomad SAS

AF:

0.621

Gnomad FIN

AF:

0.481

Gnomad MID

AF:

0.668

Gnomad NFE

AF:

0.455

Gnomad OTH

AF:

0.587

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

GnomAD4 genome

AF:

0.562

AC:

85512

AN:

152128

Hom.:

25124

Cov.:

AF XY:

0.565

AC XY:

42017

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.698

AC:

28948

AN:

41486

American (AMR)

AF:

0.673

AC:

10292

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.566

AC:

1960

AN:

3464

East Asian (EAS)

AF:

0.674

AC:

3495

AN:

5188

South Asian (SAS)

AF:

0.620

AC:

2990

AN:

4824

European-Finnish (FIN)

AF:

0.481

AC:

5089

AN:

10578

Middle Eastern (MID)

AF:

0.663

AC:

195

AN:

294

European-Non Finnish (NFE)

AF:

0.455

AC:

30909

AN:

67988

Other (OTH)

AF:

0.581

AC:

1229

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1835

3669

5504

7338

9173

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

718

1436

2154

2872

3590

<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:

0.275

Hom.:

613

Bravo

AF:

0.583

Asia WGS

AF:

0.647

AC:

2249

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.5

(source)

DANN

Benign

0.74

PhyloP100

-0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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