rs12352425

Positions:

• chr9-22042087-G-A

Variant summary

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

The NR_003529.3(CDKN2B-AS1):​n.847-4230G>A 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 0.165 in 151,944 control chromosomes in the GnomAD database, including 2,817 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 0.16 (2817 hom., cov: 32)
• Consequence: CDKN2B-AS1 NR_003529.3 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.12

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=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDKN2B-AS1	NR_003529.3	n.847-4230G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000650946.1	n.30-4664G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25035 AN: 151826 Hom.: 2815 Cov.: 32

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.0899

Gnomad EAS AF: 0.0883

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0866

Gnomad OTH AF: 0.141

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

GnomAD4 genome AF: 0.165 AC: 25060 AN: 151944 Hom.: 2817 Cov.: 32 AF XY: 0.168 AC XY: 12472 AN XY: 74264

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.271

Gnomad4 ASJ AF: 0.0899

Gnomad4 EAS AF: 0.0879

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.0866

Gnomad4 OTH AF: 0.141

Alfa AF: 0.145 Hom.: 810

Bravo AF: 0.184

Asia WGS AF: 0.175 AC: 607 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.084
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12352425; hg19: chr9-22042086;