ENST00000650946.1:n.439-1599G>C

Variant names:

• chr9-22125504-G-C
• rs1333049
• ENST00000650946.1:n.439-1599G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000650946.1(CDKN2B-AS1):​n.439-1599G>C variant causes a intron 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
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: -0.862
• Publications: 502 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000650946.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN2B-AS1	NR_185859.1		n.781-1599G>C		intron	N/A
	CDKN2B-AS1	NR_185867.1		n.1256-1599G>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN2B-AS1	ENST00000650946.1		n.439-1599G>C		intron	N/A

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

African (AFR) AF: 0.239 AC: 9907 AN: 41456

American (AMR) AF: 0.483 AC: 7383 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.577 AC: 2003 AN: 3470

East Asian (EAS) AF: 0.506 AC: 2619 AN: 5176

South Asian (SAS) AF: 0.515 AC: 2479 AN: 4810

European-Finnish (FIN) AF: 0.416 AC: 4391 AN: 10552

Middle Eastern (MID) AF: 0.551 AC: 161 AN: 292

European-Non Finnish (NFE) AF: 0.488 AC: 33134 AN: 67958

Other (OTH) AF: 0.470 AC: 992 AN: 2110

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

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

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.64
DANN	Benign	0.56
PhyloP100		-0.86

Splicing

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

Other links and lift over

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