rs1333050

Positions:

• chr9-22125914-C-T

Variant summary

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

The ENST00000650946.1(CDKN2B-AS1):​n.439-1189C>T 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 0.505 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 ENST00000650946.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.243

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.65 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.439-1189C>T		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.189

Gnomad4 AMR AF: 0.555

Gnomad4 ASJ AF: 0.699

Gnomad4 EAS AF: 0.514

Gnomad4 SAS AF: 0.525

Gnomad4 FIN AF: 0.601

Gnomad4 NFE AF: 0.655

Gnomad4 OTH AF: 0.572

Alfa AF: 0.616 Hom.: 23631

Bravo AF: 0.489

Asia WGS AF: 0.517 AC: 1800 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

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