rs1333050

Variant names:

• chr9-22125914-C-T
• rs1333050
• ENST00000650946.1:n.439-1189C>T

Variant summary

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

The NR_185859.1(CDKN2B-AS1):​n.781-1189C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 151,964 control chromosomes in the GnomAD database, including 22,424 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 0.51 (22424 hom., cov: 33)
• Consequence: CDKN2B-AS1 NR_185859.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.243
• Publications: 27 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_185859.1. 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
	CDKN2B-AS1	NR_185859.1		n.781-1189C>T		intron	N/A
	CDKN2B-AS1	NR_185867.1		n.1256-1189C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN2B-AS1	ENST00000650946.1		n.439-1189C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76761 AN: 151846 Hom.: 22425 Cov.: 33

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.601

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.655

Gnomad OTH AF: 0.575

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

GnomAD4 genome AF: 0.505 AC: 76767 AN: 151964 Hom.: 22424 Cov.: 33 AF XY: 0.502 AC XY: 37278 AN XY: 74268

African (AFR) AF: 0.189 AC: 7831 AN: 41406

American (AMR) AF: 0.555 AC: 8482 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.699 AC: 2425 AN: 3468

East Asian (EAS) AF: 0.514 AC: 2650 AN: 5154

South Asian (SAS) AF: 0.525 AC: 2523 AN: 4808

European-Finnish (FIN) AF: 0.601 AC: 6336 AN: 10534

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.655 AC: 44519 AN: 67994

Other (OTH) AF: 0.572 AC: 1210 AN: 2114

Alfa AF: 0.602 Hom.: 59303

Bravo AF: 0.489

Asia WGS AF: 0.517 AC: 1800 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.9
DANN	Benign	0.58
PhyloP100		0.24

Splicing

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

Other links and lift over

dbSNP: rs1333050; hg19: chr9-22125913; COSMIC: COSV69592484;