rs2151280

Variant names:

• chr9-22034720-G-A
• rs2151280
• ENST00000428597.7:n.846+1734G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-22034720-G-A
• chr9-22034720-G-C
• chr9-22034720-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000428597.7(CDKN2B-AS1):​n.846+1734G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 151,790 control chromosomes in the GnomAD database, including 17,533 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 0.46 (17533 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860
• Publications: 87 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN2B-AS1	NR_003529.4	n.846+1734G>A		intron_variant	Intron 3 of 18	ENST00000428597.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000428597.7	n.846+1734G>A		intron_variant	Intron 3 of 18	1	NR_003529.4

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70565 AN: 151672 Hom.: 17538 Cov.: 32

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.674

Gnomad SAS AF: 0.632

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.641

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.519

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

GnomAD4 genome AF: 0.465 AC: 70576 AN: 151790 Hom.: 17533 Cov.: 32 AF XY: 0.472 AC XY: 35019 AN XY: 74188

African (AFR) AF: 0.315 AC: 13020 AN: 41384

American (AMR) AF: 0.641 AC: 9778 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.601 AC: 2082 AN: 3464

East Asian (EAS) AF: 0.673 AC: 3465 AN: 5146

South Asian (SAS) AF: 0.632 AC: 3046 AN: 4820

European-Finnish (FIN) AF: 0.501 AC: 5266 AN: 10518

Middle Eastern (MID) AF: 0.645 AC: 187 AN: 290

European-Non Finnish (NFE) AF: 0.474 AC: 32186 AN: 67900

Other (OTH) AF: 0.515 AC: 1087 AN: 2110

Alfa AF: 0.467 Hom.: 35907

Bravo AF: 0.468

Asia WGS AF: 0.620 AC: 2154 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.1
DANN	Benign	0.71
PhyloP100		-0.086

Splicing

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

Other links and lift over

dbSNP: rs2151280; hg19: chr9-22034719; COSMIC: COSV68676812;