9-22043927-A-G

Variant names:

• chr9-22043927-A-G
• rs1412829
• ENST00000428597.7:n.847-2390A>G

GermlineCancer (beta)

Variant summary

Our verdict is Benign.

<-10 Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.908
• Publications: 118 publications found

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]

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Benign. The variant received -12 points.

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

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

CDKN2B-AS1 NR_003529.4

MANE Select

HGVSc / HGVSpn.847-2390A>G

Exon rankIntron 3 of 18

intron

Prot:

CDKN2B-AS1 NR_047532.2

HGVSc / HGVSpn.534-2390A>G

Exon rankIntron 2 of 13

intron

Prot:

CDKN2B-AS1 NR_047533.2

HGVSc / HGVSpn.372-2824A>G

Exon rankIntron 1 of 3

intron

Prot:

Ensembl Transcripts

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

CDKN2B-AS1 ENST00000428597.7

TSL:1MANE Select

HGVSc / HGVSpn.847-2390A>G

Exon rankIntron 3 of 18

intron

Prot:

CDKN2B-AS1 ENST00000455933.8

TSL:1

HGVSc / HGVSpn.341-2824A>G

Exon rankIntron 1 of 4

intron

Prot:

CDKN2B-AS1 ENST00000577551.5

TSL:1

HGVSc / HGVSpn.261-2824A>G

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 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

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
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.

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.

Other links and lift over

dbSNP: rs1412829;

hg19: chr9-22043926;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar