Genetic Variant CDKN2B-AS1:n.2448+5949G>C (chr9-22072302-G-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.2448+5949G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 152,130 control chromosomes in the GnomAD database, including 32,625 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as protective (no stars).

Frequency

Genomes: 𝑓 0.63 ( 32625 hom., cov: 33)

Consequence

CDKN2B-AS1
ENST00000428597.7 intron

Scores

Clinical Significance

protective no assertion criteria provided B:1

Conservation

PhyloP100: -0.395

Publications

50 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=-0.95).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.898 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.2448+5949G>C	intron	N/A
CDKN2B-AS1	NR_047532.2		n.1075+15915G>C	intron	N/A
CDKN2B-AS1	NR_047533.2		n.645-5377G>C	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.2448+5949G>C	intron	N/A
CDKN2B-AS1	ENST00000455933.8	TSL:1	n.750-5377G>C	intron	N/A
CDKN2B-AS1	ENST00000577551.5	TSL:1	n.533+23074G>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.629

AC:

95627

AN:

152012

Hom.:

32579

Cov.:

show subpopulations

Gnomad AFR

AF:

0.906

Gnomad AMI

AF:

0.502

Gnomad AMR

AF:

0.565

Gnomad ASJ

AF:

0.663

Gnomad EAS

AF:

0.709

Gnomad SAS

AF:

0.650

Gnomad FIN

AF:

0.438

Gnomad MID

AF:

0.744

Gnomad NFE

AF:

0.496

Gnomad OTH

AF:

0.648

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

GnomAD4 genome

AF:

0.629

AC:

95733

AN:

152130

Hom.:

32625

Cov.:

AF XY:

0.622

AC XY:

46284

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.906

AC:

37642

AN:

41558

American (AMR)

AF:

0.565

AC:

8630

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.663

AC:

2303

AN:

3472

East Asian (EAS)

AF:

0.709

AC:

3668

AN:

5174

South Asian (SAS)

AF:

0.649

AC:

3125

AN:

4814

European-Finnish (FIN)

AF:

0.438

AC:

4623

AN:

10556

Middle Eastern (MID)

AF:

0.738

AC:

217

AN:

294

European-Non Finnish (NFE)

AF:

0.496

AC:

33706

AN:

67958

Other (OTH)

AF:

0.644

AC:

1361

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1614

3227

4841

6454

8068

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

764

1528

2292

3056

3820

<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:

0.400

Hom.:

1065

Bravo

AF:

0.647

Asia WGS

AF:

0.677

AC:

2353

AN:

3478

ClinVar

ClinVar submissions

Significance:protective

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

-0.95

CADD

Benign

7.3

(source)

DANN

Benign

0.76

PhyloP100

-0.40

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