dbSNP rs1333045: CDKN2B-AS1:n.3032+429T>C (chr9-22119196-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000644233.2(CDKN2B-AS1):n.229T>C 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 0.507 in 151,756 control chromosomes in the GnomAD database, including 19,474 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 0.51 ( 19474 hom., cov: 31)

Failed GnomAD Quality Control

Consequence

CDKN2B-AS1
ENST00000644233.2 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.249

Publications

86 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 ENST00000644233.2, 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=-0.89).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000644233.2. 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.3032+429T>C	intron	N/A
CDKN2B-AS1	NR_047532.2		n.1821+429T>C	intron	N/A
CDKN2B-AS1	NR_047534.2		n.1085+429T>C	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.3032+429T>C	intron	N/A
CDKN2B-AS1	ENST00000422420.3	TSL:1	n.300-1004T>C	intron	N/A
CDKN2B-AS1	ENST00000577551.5	TSL:1	n.733+429T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.507

AC:

76872

AN:

151638

Hom.:

19462

Cov.:

show subpopulations

Gnomad AFR

AF:

0.472

Gnomad AMI

AF:

0.491

Gnomad AMR

AF:

0.525

Gnomad ASJ

AF:

0.614

Gnomad EAS

AF:

0.519

Gnomad SAS

AF:

0.542

Gnomad FIN

AF:

0.458

Gnomad MID

AF:

0.585

Gnomad NFE

AF:

0.521

Gnomad OTH

AF:

0.555

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.507

AC:

76912

AN:

151756

Hom.:

19474

Cov.:

AF XY:

0.501

AC XY:

37128

AN XY:

74132

show subpopulations

African (AFR)

AF:

0.471

AC:

19500

AN:

41362

American (AMR)

AF:

0.526

AC:

8001

AN:

15222

Ashkenazi Jewish (ASJ)

AF:

0.614

AC:

2132

AN:

3470

East Asian (EAS)

AF:

0.519

AC:

2675

AN:

5156

South Asian (SAS)

AF:

0.541

AC:

2596

AN:

4802

European-Finnish (FIN)

AF:

0.458

AC:

4813

AN:

10510

Middle Eastern (MID)

AF:

0.588

AC:

173

AN:

294

European-Non Finnish (NFE)

AF:

0.521

AC:

35419

AN:

67926

Other (OTH)

AF:

0.549

AC:

1157

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1905

3810

5715

7620

9525

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

702

1404

2106

2808

3510

<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:

0.511

Hom.:

33425

Bravo

AF:

0.508

Asia WGS

AF:

0.521

AC:

1814

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

4.7

(source)

DANN

Benign

0.75

PhyloP100

-0.25

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