dbSNP rs4977574: CDKN2B-AS1:n.2698+1211A>G (chr9-22098575-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+1211A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 152,068 control chromosomes in the GnomAD database, including 13,949 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

Frequency

Genomes: 𝑓 0.40 ( 13949 hom., cov: 32)

Consequence

CDKN2B-AS1
ENST00000428597.7 intron

Scores

Clinical Significance

risk factor no assertion criteria provided O:1

Conservation

PhyloP100: -0.0800

Publications

316 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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new If you want to explore the variant's impact on the transcript ENST00000428597.7, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.74).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000428597.7. 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.2698+1211A>G	intron	N/A
CDKN2B-AS1	NR_047532.2		n.1487+1211A>G	intron	N/A
CDKN2B-AS1	NR_047534.2		n.751+1211A>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.2698+1211A>G	intron	N/A
CDKN2B-AS1	ENST00000577551.5	TSL:1	n.534-13745A>G	intron	N/A
CDKN2B-AS1	ENST00000580576.6	TSL:1	n.1487+1211A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.405

AC:

61532

AN:

151950

Hom.:

13962

Cov.:

show subpopulations

Gnomad AFR

AF:

0.182

Gnomad AMI

AF:

0.495

Gnomad AMR

AF:

0.451

Gnomad ASJ

AF:

0.623

Gnomad EAS

AF:

0.485

Gnomad SAS

AF:

0.525

Gnomad FIN

AF:

0.433

Gnomad MID

AF:

0.642

Gnomad NFE

AF:

0.496

Gnomad OTH

AF:

0.475

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

GnomAD4 genome

AF:

0.405

AC:

61534

AN:

152068

Hom.:

13949

Cov.:

AF XY:

0.402

AC XY:

29893

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.182

AC:

7563

AN:

41510

American (AMR)

AF:

0.451

AC:

6886

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.623

AC:

2159

AN:

3464

East Asian (EAS)

AF:

0.485

AC:

2505

AN:

5168

South Asian (SAS)

AF:

0.523

AC:

2517

AN:

4810

European-Finnish (FIN)

AF:

0.433

AC:

4585

AN:

10578

Middle Eastern (MID)

AF:

0.633

AC:

186

AN:

294

European-Non Finnish (NFE)

AF:

0.496

AC:

33689

AN:

67960

Other (OTH)

AF:

0.471

AC:

993

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1746

3492

5237

6983

8729

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

598

1196

1794

2392

2990

<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:

0.470

Hom.:

80431

Bravo

AF:

0.394

Asia WGS

AF:

0.490

AC:

1705

AN:

3478

ClinVar

ClinVar submissions

Significance:risk factor

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Three Vessel Coronary Disease (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

1.3

(source)

DANN

Benign

0.92

PhyloP100

-0.080

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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