rs518394

Positions:

• chr9-22019674-G-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.372-9759G>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 0.295 in 152,002 control chromosomes in the GnomAD database, including 8,575 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 0.30 (8575 hom., cov: 31)
• Consequence: CDKN2B-AS1 NR_003529.3 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07

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 = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDKN2B-AS1	NR_003529.3	n.372-9759G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDKN2B-AS1	ENST00000650946.1	n.29+24513G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44881 AN: 151884 Hom.: 8568 Cov.: 31

Gnomad AFR AF: 0.0762

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.295 AC: 44889 AN: 152002 Hom.: 8575 Cov.: 31 AF XY: 0.293 AC XY: 21800 AN XY: 74282

Gnomad4 AFR AF: 0.0761

Gnomad4 AMR AF: 0.226

Gnomad4 ASJ AF: 0.324

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.432

Gnomad4 NFE AF: 0.437

Gnomad4 OTH AF: 0.286

Alfa AF: 0.376 Hom.: 1704

Bravo AF: 0.272

Asia WGS AF: 0.210 AC: 733 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	6.7
DANN	Benign	0.68

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: rs518394; hg19: chr9-22019673;