dbSNP rs77728904: CDKN2B-AS1:n.1389-828A>C (chr9-22057531-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.1389-828A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0759 in 152,270 control chromosomes in the GnomAD database, including 439 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 0.076 ( 439 hom., cov: 32)

Consequence

CDKN2B-AS1
ENST00000428597.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.630

Publications

11 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=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0901 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.1389-828A>C	intron	N/A
CDKN2B-AS1	NR_047532.2		n.1075+1144A>C	intron	N/A
CDKN2B-AS1	NR_047533.2		n.644+8303A>C	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.1389-828A>C	intron	N/A
CDKN2B-AS1	ENST00000455933.8	TSL:1	n.749+1144A>C	intron	N/A
CDKN2B-AS1	ENST00000577551.5	TSL:1	n.533+8303A>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0759

AC:

11543

AN:

152152

Hom.:

438

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0924

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.0602

Gnomad ASJ

AF:

0.0808

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0366

Gnomad FIN

AF:

0.0759

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.0781

Gnomad OTH

AF:

0.0760

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

GnomAD4 genome

AF:

0.0759

AC:

11558

AN:

152270

Hom.:

439

Cov.:

AF XY:

0.0745

AC XY:

5550

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.0925

AC:

3845

AN:

41562

American (AMR)

AF:

0.0601

AC:

919

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0808

AC:

280

AN:

3466

East Asian (EAS)

AF:

0.00135

AC:

AN:

5186

South Asian (SAS)

AF:

0.0369

AC:

178

AN:

4830

European-Finnish (FIN)

AF:

0.0759

AC:

805

AN:

10610

Middle Eastern (MID)

AF:

0.119

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0781

AC:

5310

AN:

68010

Other (OTH)

AF:

0.0752

AC:

159

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

557

1114

1671

2228

2785

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

134

268

402

536

670

<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:

0.0592

Hom.:

Bravo

AF:

0.0743

Asia WGS

AF:

0.0310

AC:

109

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

2.7

(source)

DANN

Benign

0.72

PhyloP100

0.63

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