chr9-22133252-G-A

Variant names:

• chr9-22133252-G-A
• rs7045889
• ENST00000755351.1:n.302+5850G>A

Variant summary

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

The ENST00000755351.1(CDKN2B-AS1):​n.302+5850G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 151,984 control chromosomes in the GnomAD database, including 25,625 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 0.58 (25625 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000755351.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29
• Publications: 18 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000755351.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN2B-AS1	ENST00000755351.1		n.302+5850G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87814 AN: 151868 Hom.: 25616 Cov.: 32

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.711

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.670

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.611

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

GnomAD4 genome AF: 0.578 AC: 87858 AN: 151984 Hom.: 25625 Cov.: 32 AF XY: 0.581 AC XY: 43128 AN XY: 74292

African (AFR) AF: 0.509 AC: 21067 AN: 41410

American (AMR) AF: 0.541 AC: 8261 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.648 AC: 2248 AN: 3468

East Asian (EAS) AF: 0.712 AC: 3686 AN: 5180

South Asian (SAS) AF: 0.605 AC: 2915 AN: 4818

European-Finnish (FIN) AF: 0.670 AC: 7068 AN: 10548

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.596 AC: 40538 AN: 67964

Other (OTH) AF: 0.612 AC: 1291 AN: 2108

Alfa AF: 0.587 Hom.: 78840

Bravo AF: 0.566

Asia WGS AF: 0.647 AC: 2247 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	9.6
DANN	Benign	0.76
PhyloP100		1.3

Splicing

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

Other links and lift over

dbSNP: rs7045889; hg19: chr9-22133251; COSMIC: COSV69451074;