Genetic Variant 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 ENST00000428597.7(CDKN2B-AS1):n.2698+6450A>G variant causes a intron 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
ENST00000428597.7 intron

Scores

Clinical Significance

protective no assertion criteria provided B:1

Conservation

PhyloP100: -0.0830

Publications

93 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=-0.83).

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
CDKN2B-AS1	NR_003529.4 link	n.2698+6450A>G	intron_variant	Intron 14 of 18
CDKN2B-AS1	NR_047532.2 link	n.1487+6450A>G	intron_variant	Intron 9 of 13
CDKN2B-AS1	NR_047534.2 link	n.751+6450A>G	intron_variant	Intron 4 of 8

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
CDKN2B-AS1	ENST00000428597.7 link	n.2698+6450A>G	intron_variant	Intron 14 of 18	1
CDKN2B-AS1	ENST00000577551.5 link	n.534-8506A>G	intron_variant	Intron 3 of 6	1
CDKN2B-AS1	ENST00000580576.6 link	n.1487+6450A>G	intron_variant	Intron 9 of 13	1

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

Significance: protective

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Three Vessel Coronary Disease

Benign:1

Department of Cardiology, Chinese Academy of Medical Sciences, Fuwai Hospital

Significance:protective

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over