9-22124478-A-G

Position:

• chr9-22124478-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.439-2625A>G 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 0.405 in 151,872 control chromosomes in the GnomAD database, including 13,708 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 0.40 (13708 hom., cov: 33)
• Consequence: CDKN2B-AS1 ENST00000650946.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0760

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=-0.75).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.508 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.439-2625A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61496 AN: 151754 Hom.: 13714 Cov.: 33

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.468

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

GnomAD4 genome AF: 0.405 AC: 61504 AN: 151872 Hom.: 13708 Cov.: 33 AF XY: 0.402 AC XY: 29839 AN XY: 74214

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.479

Gnomad4 ASJ AF: 0.586

Gnomad4 EAS AF: 0.507

Gnomad4 SAS AF: 0.525

Gnomad4 FIN AF: 0.412

Gnomad4 NFE AF: 0.486

Gnomad4 OTH AF: 0.463

Alfa AF: 0.477 Hom.: 22598

Bravo AF: 0.399

Asia WGS AF: 0.495 AC: 1721 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	9.9
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10757278; hg19: chr9-22124477; COSMIC: COSV69592462;