rs13298881

Positions:

• chr9-22012052-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NR_003529.3(CDKN2B-AS1):​n.371+16891T>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 0.0808 in 582,954 control chromosomes in the GnomAD database, including 2,323 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 0.076 (588 hom., cov: 32)
  • Exomes 𝑓: 0.082 (1735 hom.)
• Consequence: CDKN2B-AS1 NR_003529.3 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.60

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDKN2B-AS1	NR_003529.3	n.371+16891T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000650946.1	n.29+16891T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0763 AC: 11612 AN: 152134 Hom.: 589 Cov.: 32

Gnomad AFR AF: 0.0387

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.0880

Gnomad ASJ AF: 0.0813

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0240

Gnomad FIN AF: 0.0643

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.0919

GnomAD4 exome AF: 0.0825 AC: 35517 AN: 430702 Hom.: 1735 AF XY: 0.0800 AC XY: 18175 AN XY: 227286

Gnomad4 AFR exome AF: 0.0375

Gnomad4 AMR exome AF: 0.0768

Gnomad4 ASJ exome AF: 0.0819

Gnomad4 EAS exome AF: 0.0000698

Gnomad4 SAS exome AF: 0.0268

Gnomad4 FIN exome AF: 0.0699

Gnomad4 NFE exome AF: 0.105

Gnomad4 OTH exome AF: 0.0879

GnomAD4 genome AF: 0.0763 AC: 11611 AN: 152252 Hom.: 588 Cov.: 32 AF XY: 0.0715 AC XY: 5327 AN XY: 74460

Gnomad4 AFR AF: 0.0386

Gnomad4 AMR AF: 0.0879

Gnomad4 ASJ AF: 0.0813

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0236

Gnomad4 FIN AF: 0.0643

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.0914

Alfa AF: 0.104 Hom.: 1233

Bravo AF: 0.0792

Asia WGS AF: 0.0140 AC: 49 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	11
DANN	Benign	0.94

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: rs13298881; hg19: chr9-22012051;