rs564398

Positions:

• chr9-22029548-T-C

Variant summary

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

The NR_003529.3(CDKN2B-AS1):​n.487T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 778,638 control chromosomes in the GnomAD database, including 48,582 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 0.28 (7706 hom., cov: 32)
  • Exomes 𝑓: 0.34 (40876 hom.)
• Consequence: CDKN2B-AS1 NR_003529.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.156

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDKN2B-AS1	NR_003529.3	n.487T>C		non_coding_transcript_exon_variant	2/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000650946.1	n.30-17203T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42493 AN: 151930 Hom.: 7700 Cov.: 32

Gnomad AFR AF: 0.0730

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.263

GnomAD3 exomes AF: 0.310 AC: 75443 AN: 243314 Hom.: 14061 AF XY: 0.317 AC XY: 42322 AN XY: 133386

Gnomad AFR exome AF: 0.0628

Gnomad AMR exome AF: 0.162

Gnomad ASJ exome AF: 0.284

Gnomad EAS exome AF: 0.112

Gnomad SAS exome AF: 0.257

Gnomad FIN exome AF: 0.416

Gnomad NFE exome AF: 0.416

Gnomad OTH exome AF: 0.327

GnomAD4 exome AF: 0.343 AC: 214932 AN: 626590 Hom.: 40876 Cov.: 0 AF XY: 0.341 AC XY: 116419 AN XY: 341414

Gnomad4 AFR exome AF: 0.0697

Gnomad4 AMR exome AF: 0.169

Gnomad4 ASJ exome AF: 0.284

Gnomad4 EAS exome AF: 0.134

Gnomad4 SAS exome AF: 0.256

Gnomad4 FIN exome AF: 0.414

Gnomad4 NFE exome AF: 0.413

Gnomad4 OTH exome AF: 0.330

GnomAD4 genome AF: 0.280 AC: 42501 AN: 152048 Hom.: 7706 Cov.: 32 AF XY: 0.278 AC XY: 20678 AN XY: 74270

Gnomad4 AFR AF: 0.0728

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.282

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.249

Gnomad4 FIN AF: 0.411

Gnomad4 NFE AF: 0.414

Gnomad4 OTH AF: 0.268

Alfa AF: 0.373 Hom.: 22400

Bravo AF: 0.257

Asia WGS AF: 0.204 AC: 713 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.8
DANN	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs564398; hg19: chr9-22029547;