dbSNP rs7049105: CDKN2B-AS1:n.372-631A>G (chr9-22028802-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.372-631A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 151,930 control chromosomes in the GnomAD database, including 26,689 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 0.58 ( 26689 hom., cov: 32)

Consequence

CDKN2B-AS1
ENST00000428597.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.328

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=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.703 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.372-631A>G	intron	N/A
CDKN2B-AS1	NR_047532.2		n.372-631A>G	intron	N/A
CDKN2B-AS1	NR_047533.2		n.372-17949A>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.372-631A>G	intron	N/A
CDKN2B-AS1	ENST00000455933.8	TSL:1	n.341-17949A>G	intron	N/A
CDKN2B-AS1	ENST00000577551.5	TSL:1	n.261-17949A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.582

AC:

88294

AN:

151812

Hom.:

26663

Cov.:

show subpopulations

Gnomad AFR

AF:

0.710

Gnomad AMI

AF:

0.503

Gnomad AMR

AF:

0.689

Gnomad ASJ

AF:

0.607

Gnomad EAS

AF:

0.676

Gnomad SAS

AF:

0.639

Gnomad FIN

AF:

0.502

Gnomad MID

AF:

0.677

Gnomad NFE

AF:

0.479

Gnomad OTH

AF:

0.608

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

GnomAD4 genome

AF:

0.582

AC:

88371

AN:

151930

Hom.:

26689

Cov.:

AF XY:

0.584

AC XY:

43355

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.710

AC:

29454

AN:

41480

American (AMR)

AF:

0.689

AC:

10512

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.607

AC:

2106

AN:

3468

East Asian (EAS)

AF:

0.675

AC:

3497

AN:

5180

South Asian (SAS)

AF:

0.638

AC:

3068

AN:

4810

European-Finnish (FIN)

AF:

0.502

AC:

5296

AN:

10546

Middle Eastern (MID)

AF:

0.677

AC:

199

AN:

294

European-Non Finnish (NFE)

AF:

0.479

AC:

32512

AN:

67874

Other (OTH)

AF:

0.602

AC:

1270

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1799

3598

5397

7196

8995

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

740

1480

2220

2960

3700

<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:

0.521

Hom.:

55913

Bravo

AF:

0.602

Asia WGS

AF:

0.656

AC:

2275

AN:

3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

4.7

(source)

DANN

Benign

0.87

PhyloP100

0.33

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