Genetic Variant CDKN2B-AS1:n.847-2390A>T (chr9-22043927-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is The variant received -2 classification points (ACMG Germline Pathogenicity v2019). PM2BP4_Strong

The NR_003529.4(CDKN2B-AS1):n.847-2390A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

CDKN2B-AS1
NR_003529.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.908

Publications

0 publications found

Variant links:

Genes affected

CDKN2B-AS1 (HGNC:34341): (CDKN2B and CDKN2A antisense cis and trans regulatory 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 NR_003529.4, 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.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Likely_benign. The variant received -2 points.

Show applied only (2)

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM2Absent/extremely low in population databases		Absent from gnomAD (AR/unknown gene) — PM2; Absent from gnomAD at well-covered site (MOI: unknown) (threshold 0.001) — PM2 moderate.
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); No splicing predictor data available.; Germline computational verdict: benign (Strong).

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NR_003529.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
CDKN2B-AS1 NR_003529.4	MANE Select	n.847-2390A>T	intron	Intron 3 of 18	Prot:
CDKN2B-AS1 NR_047532.2		n.534-2390A>T	intron	Intron 2 of 13	Prot:
CDKN2B-AS1 NR_047533.2		n.372-2824A>T	intron	Intron 1 of 3	Prot:

CDKN2B-AS1 NR_003529.4

MANE Select

HGVSc / HGVSpn.847-2390A>T

Exon rankIntron 3 of 18

intron

Prot:

CDKN2B-AS1 NR_047532.2

HGVSc / HGVSpn.534-2390A>T

Exon rankIntron 2 of 13

intron

Prot:

CDKN2B-AS1 NR_047533.2

HGVSc / HGVSpn.372-2824A>T

Exon rankIntron 1 of 3

intron

Prot:

Ensembl Transcripts

Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
CDKN2B-AS1 ENST00000428597.7	TSL:1MANE Select	n.847-2390A>T	intron	Intron 3 of 18	Prot:
CDKN2B-AS1 ENST00000455933.8	TSL:1	n.341-2824A>T	intron	Intron 1 of 4	Prot:
CDKN2B-AS1 ENST00000577551.5	TSL:1	n.261-2824A>T	intron	Intron 1 of 6	Prot:

CDKN2B-AS1 ENST00000428597.7

TSL:1MANE Select

HGVSc / HGVSpn.847-2390A>T

Exon rankIntron 3 of 18

intron

Prot:

CDKN2B-AS1 ENST00000455933.8

TSL:1

HGVSc / HGVSpn.341-2824A>T

Exon rankIntron 1 of 4

intron

Prot:

CDKN2B-AS1 ENST00000577551.5

TSL:1

HGVSc / HGVSpn.261-2824A>T

Exon rankIntron 1 of 6

intron

Prot:

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 2 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:32
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:32

Showing 2 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score
AlphaGenome AVI	Benign	0.30
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.25
DANN	Benign	0.40
GPN-Star LLR	N/A	0.061
GPN-Star score	N/A	-0.061
PhyloP100	Benign	-0.91

Showing 7 of 7 scores

Splicing Scores

No splicing scores have been computed for this variant.

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.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational Scores

Splicing Scores

MaveDB functional evidence ?

Publications

Other links and lift over

MaveDB functional evidence