9-22043927-A-G

Variant names:

Variant summary

Our verdict is The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

The NR_003529.4(CDKN2B-AS1):n.847-2390A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.279 (AC=42,435) in the gnomAD database across 151,872 control chromosomes, including 7,702 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.41. 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: 𝑓 0.28 ( 7702 hom., cov: 32)

Consequence

CDKN2B-AS1
NR_003529.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.908

Publications

117 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 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: Benign. The variant received -12 points.

Show applied only (2)

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	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).
	BA1Stand-alone benign allele frequency (>5%)		GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.4099 — exceeds 5%% threshold (BA1 applied)

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	Effect	Exon Rank
CDKN2B-AS1	NR_003529.4	MANE Select	n.847-2390A>G	intron	N/A
CDKN2B-AS1	NR_047532.2		n.534-2390A>G	intron	N/A
CDKN2B-AS1	NR_047533.2		n.372-2824A>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.847-2390A>G	intron	N/A
CDKN2B-AS1	ENST00000455933.8	TSL:1	n.341-2824A>G	intron	N/A
CDKN2B-AS1	ENST00000577551.5	TSL:1	n.261-2824A>G	intron	N/A

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 4 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.280	AC:42429	Hom:7696	AN:151754	Cov:32
GnomAD4 genome	AF: 0.279	AC:42435	Hom:7702	AN:151872	Cov:32
TOPMed (Bravo)	AF: 0.256	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.369	AC:229370	Hom:46174	AN:622178	Cov:
Local & regional cohorts 10 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.255	AC:597	Hom:83	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.120	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.513	AC:154	Hom:	AN:300	Cov:
GenomeAsia100K	AF: 0.204	AC:711	Hom:	AN:3474	Cov:
Korea4K (4,157 Koreans)	AF: 0.134	AC:971	Hom:	AN:7226	Cov:
Qatari Genome	AF: 0.224	AC:39	Hom:	AN:174	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.158	AC:19248	Hom:1534	AN:122042	Cov:
Turkish Variome	AF: 0.290	AC:448	Hom:66	AN:1546	Cov:
UK10K	AF: 0.421	AC:3181	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.112	AC:1001	Hom:60	AN:8960	Cov:

Showing 14 sources

Tested, but no data found:GnomAD4 exomeIf GnomAD4 is missing, the position is probably not covered by the project.

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score
AlphaGenome AVI	Benign	0.41
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.32
DANN	Benign	0.55
GPN-Star LLR	N/A	2.2
GPN-Star score	N/A	-1.5
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.

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

Publications

Other links and lift over