rs1333048

Variant names:

• chr9-22125348-A-C
• rs1333048
• ENST00000650946.1:n.439-1755A>C

Your query was ambiguous. Multiple possible variants found:

• chr9-22125348-A-C
• chr9-22125348-A-G

Variant summary

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

The ENST00000650946.1(CDKN2B-AS1):​n.439-1755A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 152,114 control chromosomes in the GnomAD database, including 15,825 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 0.45 (15825 hom., cov: 33)
• Consequence: CDKN2B-AS1 ENST00000650946.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.371
• Publications: 121 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN2B-AS1	NR_185859.1	n.781-1755A>C		intron_variant	Intron 4 of 4
CDKN2B-AS1	NR_185867.1	n.1256-1755A>C		intron_variant	Intron 6 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000650946.1	n.439-1755A>C		intron_variant	Intron 4 of 4

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67730 AN: 151996 Hom.: 15831 Cov.: 33

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.669

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.445 AC: 67740 AN: 152114 Hom.: 15825 Cov.: 33 AF XY: 0.441 AC XY: 32776 AN XY: 74376

African (AFR) AF: 0.291 AC: 12063 AN: 41504

American (AMR) AF: 0.512 AC: 7822 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.627 AC: 2176 AN: 3470

East Asian (EAS) AF: 0.512 AC: 2651 AN: 5176

South Asian (SAS) AF: 0.543 AC: 2615 AN: 4818

European-Finnish (FIN) AF: 0.417 AC: 4406 AN: 10578

Middle Eastern (MID) AF: 0.654 AC: 191 AN: 292

European-Non Finnish (NFE) AF: 0.505 AC: 34297 AN: 67968

Other (OTH) AF: 0.506 AC: 1067 AN: 2110

Alfa AF: 0.485 Hom.: 64500

Bravo AF: 0.442

Asia WGS AF: 0.512 AC: 1783 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.0
DANN	Benign	0.69
PhyloP100		0.37

Splicing

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

Other links and lift over

dbSNP: rs1333048; hg19: chr9-22125347; COSMIC: COSV69592479;