9-22125504-G-C

Position:

• chr9-22125504-G-C

Variant summary

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

The ENST00000650946.1(CDKN2B-AS1):​n.439-1599G>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 0.418 in 152,018 control chromosomes in the GnomAD database, including 14,200 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency: Genomes: 𝑓 0.42 (14200 hom., cov: 33)
• Consequence: CDKN2B-AS1 ENST00000650946.1 intron, non_coding_transcript
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: -0.862

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=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.498 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.439-1599G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63547 AN: 151902 Hom.: 14202 Cov.: 33

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.534

Gnomad AMR AF: 0.483

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.506

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.475

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

GnomAD4 genome AF: 0.418 AC: 63553 AN: 152018 Hom.: 14200 Cov.: 33 AF XY: 0.414 AC XY: 30782 AN XY: 74292

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.483

Gnomad4 ASJ AF: 0.577

Gnomad4 EAS AF: 0.506

Gnomad4 SAS AF: 0.515

Gnomad4 FIN AF: 0.416

Gnomad4 NFE AF: 0.488

Gnomad4 OTH AF: 0.470

Alfa AF: 0.472 Hom.: 9638

Bravo AF: 0.412

Asia WGS AF: 0.493 AC: 1714 AN: 3478

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Three Vessel Coronary Disease Other:1

risk factor, no assertion criteria provided

clinical testing

Department of Cardiology, Chinese Academy of Medical Sciences, Fuwai Hospital

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.64
DANN	Benign	0.56

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1333049; hg19: chr9-22125503; COSMIC: COSV69592483;