rs1333048

Positions:

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

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000650946.1(CDKN2B-AS1):​n.439-1755A>C variant causes a intron, non coding transcript 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, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.371

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000650946.1	n.439-1755A>C		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.291

Gnomad4 AMR AF: 0.512

Gnomad4 ASJ AF: 0.627

Gnomad4 EAS AF: 0.512

Gnomad4 SAS AF: 0.543

Gnomad4 FIN AF: 0.417

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.506

Alfa AF: 0.498 Hom.: 25440

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

Splicing

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

Publications

LitVar

Other links and lift over

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