Genetic Variant CDKN2B-AS1:n.371+14844T>G (chr9-22010005-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The ENST00000428597.7(CDKN2B-AS1):n.371+14844T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.017 in 152,146 control chromosomes in the GnomAD database, including 43 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 0.017 ( 43 hom., cov: 32)

Consequence

CDKN2B-AS1
ENST00000428597.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.230

Publications

15 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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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=-0.66).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.017 (2583/152146) while in subpopulation NFE AF = 0.0212 (1442/68000). AF 95% confidence interval is 0.0203. There are 43 homozygotes in GnomAd4. There are 1291 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 43 gene

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+14844T>G	intron	N/A
CDKN2B-AS1	NR_047532.2		n.371+14844T>G	intron	N/A
CDKN2B-AS1	NR_047533.2		n.371+14844T>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.371+14844T>G	intron	N/A
CDKN2B-AS1	ENST00000455933.8	TSL:1	n.340+14844T>G	intron	N/A
CDKN2B-AS1	ENST00000577551.5	TSL:1	n.260+14844T>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0170

AC:

2582

AN:

152028

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00341

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0185

Gnomad ASJ

AF:

0.0571

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00518

Gnomad FIN

AF:

0.0386

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0212

Gnomad OTH

AF:

0.0273

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

GnomAD4 genome

AF:

0.0170

AC:

2583

AN:

152146

Hom.:

Cov.:

AF XY:

0.0174

AC XY:

1291

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.00342

AC:

142

AN:

41522

American (AMR)

AF:

0.0184

AC:

282

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0571

AC:

198

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00539

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0386

AC:

407

AN:

10554

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0212

AC:

1442

AN:

68000

Other (OTH)

AF:

0.0270

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

127

254

380

507

634

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<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:

0.00831

Hom.:

379

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

6.3

(source)

DANN

Benign

0.82

PhyloP100

-0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

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