dbSNP rs1333042: CDKN2B-AS1:n.2698+6450A>G (chr9-22103814-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 ENST00000806150.1(CDKN2B-AS1):n.1002A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 151,988 control chromosomes in the GnomAD database, including 32,190 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as protective (no stars).

Frequency

Genomes: 𝑓 0.63 ( 32190 hom., cov: 31)

Consequence

CDKN2B-AS1
ENST00000806150.1 non_coding_transcript_exon

Scores

Clinical Significance

protective no assertion criteria provided B:1

Conservation

PhyloP100: -0.0830

Publications

96 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 ENST00000806150.1, 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=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000806150.1. 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+6450A>G	intron	N/A
CDKN2B-AS1	NR_047532.2		n.1487+6450A>G	intron	N/A
CDKN2B-AS1	NR_047534.2		n.751+6450A>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.2698+6450A>G	intron	N/A
CDKN2B-AS1	ENST00000577551.5	TSL:1	n.534-8506A>G	intron	N/A
CDKN2B-AS1	ENST00000580576.6	TSL:1	n.1487+6450A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.627

AC:

95233

AN:

151870

Hom.:

32144

Cov.:

show subpopulations

Gnomad AFR

AF:

0.893

Gnomad AMI

AF:

0.497

Gnomad AMR

AF:

0.555

Gnomad ASJ

AF:

0.661

Gnomad EAS

AF:

0.670

Gnomad SAS

AF:

0.618

Gnomad FIN

AF:

0.421

Gnomad MID

AF:

0.753

Gnomad NFE

AF:

0.509

Gnomad OTH

AF:

0.652

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

GnomAD4 genome

AF:

0.627

AC:

95337

AN:

151988

Hom.:

32190

Cov.:

AF XY:

0.619

AC XY:

45926

AN XY:

74248

show subpopulations

African (AFR)

AF:

0.893

AC:

37041

AN:

41478

American (AMR)

AF:

0.556

AC:

8476

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.661

AC:

2294

AN:

3472

East Asian (EAS)

AF:

0.670

AC:

3458

AN:

5158

South Asian (SAS)

AF:

0.616

AC:

2963

AN:

4808

European-Finnish (FIN)

AF:

0.421

AC:

4433

AN:

10528

Middle Eastern (MID)

AF:

0.748

AC:

220

AN:

294

European-Non Finnish (NFE)

AF:

0.510

AC:

34631

AN:

67968

Other (OTH)

AF:

0.648

AC:

1368

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1569

3138

4707

6276

7845

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

766

1532

2298

3064

3830

<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:

0.547

Hom.:

70637

Bravo

AF:

0.646

Asia WGS

AF:

0.633

AC:

2202

AN:

3478

ClinVar

ClinVar submissions

Significance:protective

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Three Vessel Coronary Disease (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.75

(source)

DANN

Benign

0.54

PhyloP100

-0.083

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