dbSNP rs10120688: CDKN2B-AS1:n.1388+113G>A (chr9-22056500-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NR_185852.1(CDKN2B-AS1):n.1055G>A 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 0.502 in 151,762 control chromosomes in the GnomAD database, including 19,726 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 0.50 ( 19721 hom., cov: 29)

Exomes 𝑓: 0.40 ( 5 hom. )

Consequence

CDKN2B-AS1
NR_185852.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.268

Publications

60 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=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_185852.1. 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.1388+113G>A	intron	N/A
CDKN2B-AS1	NR_185852.1		n.1055G>A	non_coding_transcript_exon	Exon 5 of 5
CDKN2B-AS1	NR_185856.1		n.1188G>A	non_coding_transcript_exon	Exon 6 of 6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.1388+113G>A	intron	N/A
CDKN2B-AS1	ENST00000455933.8	TSL:1	n.749+113G>A	intron	N/A
CDKN2B-AS1	ENST00000577551.5	TSL:1	n.533+7272G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.503

AC:

76169

AN:

151564

Hom.:

19718

Cov.:

show subpopulations

Gnomad AFR

AF:

0.420

Gnomad AMI

AF:

0.503

Gnomad AMR

AF:

0.660

Gnomad ASJ

AF:

0.612

Gnomad EAS

AF:

0.688

Gnomad SAS

AF:

0.638

Gnomad FIN

AF:

0.484

Gnomad MID

AF:

0.636

Gnomad NFE

AF:

0.489

Gnomad OTH

AF:

0.542

GnomAD4 exome

AF:

0.402

AC:

AN:

Hom.:

AF XY:

0.417

AC XY:

AN XY:

show subpopulations

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)

AF:

0.394

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.417

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.502

AC:

76184

AN:

151680

Hom.:

19721

Cov.:

AF XY:

0.506

AC XY:

37493

AN XY:

74096

show subpopulations

African (AFR)

AF:

0.419

AC:

17325

AN:

41302

American (AMR)

AF:

0.660

AC:

10069

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.612

AC:

2120

AN:

3464

East Asian (EAS)

AF:

0.687

AC:

3532

AN:

5144

South Asian (SAS)

AF:

0.637

AC:

3060

AN:

4802

European-Finnish (FIN)

AF:

0.484

AC:

5091

AN:

10516

Middle Eastern (MID)

AF:

0.637

AC:

186

AN:

292

European-Non Finnish (NFE)

AF:

0.489

AC:

33208

AN:

67888

Other (OTH)

AF:

0.537

AC:

1134

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

1864

3728

5593

7457

9321

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

682

1364

2046

2728

3410

<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:

0.503

Hom.:

61818

Bravo

AF:

0.511

Asia WGS

AF:

0.633

AC:

2197

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.4

(source)

DANN

Benign

0.66

PhyloP100

0.27

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over