dbSNP rs3218005: CDKN2B-AS1:n.371+5087T>C (chr9-22000248-T-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.371+5087T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,104 control chromosomes in the GnomAD database, including 1,773 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 0.14 ( 1773 hom., cov: 32)

Consequence

CDKN2B-AS1
ENST00000428597.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.237

Publications

20 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:

ENSG00000264545 (HGNC:):

ENSG00000264545 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=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.231 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.371+5087T>C	intron	N/A
CDKN2B-AS1	NR_047532.2		n.371+5087T>C	intron	N/A
CDKN2B-AS1	NR_047533.2		n.371+5087T>C	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.371+5087T>C	intron	N/A
CDKN2B-AS1	ENST00000455933.8	TSL:1	n.340+5087T>C	intron	N/A
CDKN2B-AS1	ENST00000577551.5	TSL:1	n.260+5087T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.140

AC:

21256

AN:

151986

Hom.:

1765

Cov.:

show subpopulations

Gnomad AFR

AF:

0.234

Gnomad AMI

AF:

0.0242

Gnomad AMR

AF:

0.0980

Gnomad ASJ

AF:

0.110

Gnomad EAS

AF:

0.215

Gnomad SAS

AF:

0.112

Gnomad FIN

AF:

0.0832

Gnomad MID

AF:

0.162

Gnomad NFE

AF:

0.100

Gnomad OTH

AF:

0.130

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

GnomAD4 genome

AF:

0.140

AC:

21298

AN:

152104

Hom.:

1773

Cov.:

AF XY:

0.139

AC XY:

10338

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.235

AC:

9738

AN:

41490

American (AMR)

AF:

0.0978

AC:

1496

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.110

AC:

382

AN:

3468

East Asian (EAS)

AF:

0.216

AC:

1117

AN:

5180

South Asian (SAS)

AF:

0.113

AC:

544

AN:

4814

European-Finnish (FIN)

AF:

0.0832

AC:

882

AN:

10598

Middle Eastern (MID)

AF:

0.164

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.100

AC:

6795

AN:

67950

Other (OTH)

AF:

0.130

AC:

274

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

894

1788

2682

3576

4470

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

230

460

690

920

1150

<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:

0.110

Hom.:

1197

Bravo

AF:

0.143

Asia WGS

AF:

0.144

AC:

501

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

4.1

(source)

DANN

Benign

0.60

PhyloP100

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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