dbSNP rs7341786: CDKN2B-AS1:n.2699-78A>C (chr9-22112242-A-C) – 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.2699-78A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 152,068 control chromosomes in the GnomAD database, including 33,600 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 0.64 ( 33593 hom., cov: 31)

Exomes 𝑓: 0.55 ( 7 hom. )

Consequence

CDKN2B-AS1
ENST00000428597.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.778

Publications

32 publications found

Variant links:

COSMIC-nc: COSV69592424

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:

Genome browser will be placed here

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=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.889 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.2699-78A>C	intron	N/A
CDKN2B-AS1	NR_047532.2		n.1488-78A>C	intron	N/A
CDKN2B-AS1	NR_047534.2		n.752-78A>C	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.2699-78A>C	intron	N/A
CDKN2B-AS1	ENST00000577551.5	TSL:1	n.534-78A>C	intron	N/A
CDKN2B-AS1	ENST00000580576.6	TSL:1	n.1488-78A>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.644

AC:

97765

AN:

151906

Hom.:

33549

Cov.:

show subpopulations

Gnomad AFR

AF:

0.897

Gnomad AMI

AF:

0.498

Gnomad AMR

AF:

0.614

Gnomad ASJ

AF:

0.677

Gnomad EAS

AF:

0.673

Gnomad SAS

AF:

0.626

Gnomad FIN

AF:

0.434

Gnomad MID

AF:

0.753

Gnomad NFE

AF:

0.527

Gnomad OTH

AF:

0.665

GnomAD4 exome

AF:

0.545

AC:

AN:

Hom.:

Cov.:

AF XY:

0.464

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.529

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.644

AC:

97866

AN:

152024

Hom.:

33593

Cov.:

AF XY:

0.636

AC XY:

47213

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.897

AC:

37232

AN:

41516

American (AMR)

AF:

0.614

AC:

9381

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.677

AC:

2345

AN:

3466

East Asian (EAS)

AF:

0.673

AC:

3468

AN:

5154

South Asian (SAS)

AF:

0.625

AC:

3009

AN:

4818

European-Finnish (FIN)

AF:

0.434

AC:

4570

AN:

10536

Middle Eastern (MID)

AF:

0.748

AC:

220

AN:

294

European-Non Finnish (NFE)

AF:

0.527

AC:

35798

AN:

67952

Other (OTH)

AF:

0.660

AC:

1392

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1604

3208

4812

6416

8020

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

774

1548

2322

3096

3870

<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:

0.612

Hom.:

19347

Bravo

AF:

0.665

Asia WGS

AF:

0.640

AC:

2226

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.48

(source)

DANN

Benign

0.53

PhyloP100

-0.78

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