dbSNP rs13298881: CDKN2B-AS1:n.371+16891T>C (chr9-22012052-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The ENST00000428597.7(CDKN2B-AS1):n.371+16891T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0808 in 582,954 control chromosomes in the GnomAD database, including 2,323 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 0.076 ( 588 hom., cov: 32)

Exomes 𝑓: 0.082 ( 1735 hom. )

Consequence

CDKN2B-AS1
ENST00000428597.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.60

Publications

17 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:

UBA52P6 (HGNC:36763): (ubiquitin A-52 residue ribosomal protein fusion product 1 pseudogene 6)

UBA52P6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.26).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
CDKN2B-AS1	NR_003529.4 link	n.371+16891T>C	intron_variant	Intron 1 of 18
CDKN2B-AS1	NR_047532.2 link	n.371+16891T>C	intron_variant	Intron 1 of 13
CDKN2B-AS1	NR_047533.2 link	n.371+16891T>C	intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
CDKN2B-AS1	ENST00000428597.7 link	n.371+16891T>C	intron_variant	Intron 1 of 18	1
CDKN2B-AS1	ENST00000455933.8 link	n.340+16891T>C	intron_variant	Intron 1 of 4	1
CDKN2B-AS1	ENST00000577551.5 link	n.260+16891T>C	intron_variant	Intron 1 of 6	1

Frequencies

GnomAD3 genomes

AF:

0.0763

AC:

11612

AN:

152134

Hom.:

589

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0387

Gnomad AMI

AF:

0.177

Gnomad AMR

AF:

0.0880

Gnomad ASJ

AF:

0.0813

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0240

Gnomad FIN

AF:

0.0643

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.0919

GnomAD4 exome

AF:

0.0825

AC:

35517

AN:

430702

Hom.:

1735

AF XY:

0.0800

AC XY:

18175

AN XY:

227286

show subpopulations

African (AFR)

AF:

0.0375

AC:

434

AN:

11572

American (AMR)

AF:

0.0768

AC:

1336

AN:

17390

Ashkenazi Jewish (ASJ)

AF:

0.0819

AC:

1021

AN:

12468

East Asian (EAS)

AF:

0.0000698

AC:

AN:

28646

South Asian (SAS)

AF:

0.0268

AC:

1180

AN:

43980

European-Finnish (FIN)

AF:

0.0699

AC:

2625

AN:

37532

Middle Eastern (MID)

AF:

0.111

AC:

197

AN:

1768

European-Non Finnish (NFE)

AF:

0.105

AC:

26645

AN:

253708

Other (OTH)

AF:

0.0879

AC:

2077

AN:

23638

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

1528

3056

4585

6113

7641

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0763

AC:

11611

AN:

152252

Hom.:

588

Cov.:

AF XY:

0.0715

AC XY:

5327

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.0386

AC:

1603

AN:

41560

American (AMR)

AF:

0.0879

AC:

1344

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0813

AC:

282

AN:

3470

East Asian (EAS)

AF:

0.000578

AC:

AN:

5186

South Asian (SAS)

AF:

0.0236

AC:

114

AN:

4828

European-Finnish (FIN)

AF:

0.0643

AC:

682

AN:

10606

Middle Eastern (MID)

AF:

0.156

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.106

AC:

7184

AN:

68006

Other (OTH)

AF:

0.0914

AC:

193

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

547

1094

1641

2188

2735

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.102

Hom.:

1592

Bravo

AF:

0.0792

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Benign

0.94

PhyloP100

1.6

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

Publications

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rs13298881

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over