Genetic Variant CDKN2B-AS1:n.846+404C>T (chr9-22033390-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000652420.1(CDKN2B-AS1):n.1065C>T 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 0.0666 in 152,178 control chromosomes in the GnomAD database, including 456 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 0.067 ( 456 hom., cov: 32)

Consequence

CDKN2B-AS1
ENST00000652420.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.469

Publications

14 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 (NFE) allele frequency at 95% confidence interval = 0.0978 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000652420.1. 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.846+404C>T	intron	N/A
CDKN2B-AS1	NR_047532.2		n.533+3796C>T	intron	N/A
CDKN2B-AS1	NR_047533.2		n.372-13361C>T	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.846+404C>T	intron	N/A
CDKN2B-AS1	ENST00000455933.8	TSL:1	n.341-13361C>T	intron	N/A
CDKN2B-AS1	ENST00000577551.5	TSL:1	n.261-13361C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0667

AC:

10136

AN:

152060

Hom.:

456

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0181

Gnomad AMI

AF:

0.246

Gnomad AMR

AF:

0.0580

Gnomad ASJ

AF:

0.0954

Gnomad EAS

AF:

0.000580

Gnomad SAS

AF:

0.0298

Gnomad FIN

AF:

0.0784

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0999

Gnomad OTH

AF:

0.0779

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0666

AC:

10138

AN:

152178

Hom.:

456

Cov.:

AF XY:

0.0651

AC XY:

4844

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.0181

AC:

750

AN:

41548

American (AMR)

AF:

0.0580

AC:

886

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.0954

AC:

331

AN:

3468

East Asian (EAS)

AF:

0.000581

AC:

AN:

5160

South Asian (SAS)

AF:

0.0300

AC:

145

AN:

4828

European-Finnish (FIN)

AF:

0.0784

AC:

830

AN:

10588

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0998

AC:

6787

AN:

67998

Other (OTH)

AF:

0.0785

AC:

166

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

490

981

1471

1962

2452

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

232

348

464

580

<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:

0.0775

Hom.:

297

Bravo

AF:

0.0643

Asia WGS

AF:

0.0310

AC:

107

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

0.96

(source)

DANN

Benign

0.69

PhyloP100

-0.47

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