dbSNP rs1333045: CDKN2B-AS1:n.300-1004T>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 ENST00000422420.3(CDKN2B-AS1):n.300-1004T>C variant causes a intron 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
ENST00000422420.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.249

Publications

84 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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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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
CDKN2B-AS1	NR_003529.4 link	n.3032+429T>C	intron_variant	Intron 17 of 18
CDKN2B-AS1	NR_047532.2 link	n.1821+429T>C	intron_variant	Intron 12 of 13
CDKN2B-AS1	NR_047534.2 link	n.1085+429T>C	intron_variant	Intron 7 of 8

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
CDKN2B-AS1	ENST00000422420.3 link	n.300-1004T>C	intron_variant	Intron 1 of 2	1
CDKN2B-AS1	ENST00000428597.7 link	n.3032+429T>C	intron_variant	Intron 17 of 18	1
CDKN2B-AS1	ENST00000577551.5 link	n.733+429T>C	intron_variant	Intron 5 of 6	1

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 v4.3

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over