9-22124505-A-T

Variant names:

• chr9-22124505-A-T
• rs1333047
• ENST00000650946.1:n.439-2598A>T

Variant summary

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

The ENST00000650946.1(CDKN2B-AS1):​n.439-2598A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 152,098 control chromosomes in the GnomAD database, including 32,184 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 0.63 (32184 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000650946.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.718
• Publications: 46 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN2B-AS1	NR_185859.1	n.781-2598A>T		intron_variant	Intron 4 of 4
CDKN2B-AS1	NR_185867.1	n.1256-2598A>T		intron_variant	Intron 6 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000650946.1	n.439-2598A>T		intron_variant	Intron 4 of 4

Frequencies

GnomAD3 genomes AF: 0.626 AC: 95200 AN: 151980 Hom.: 32129 Cov.: 32

Gnomad AFR AF: 0.897

Gnomad AMI AF: 0.495

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.625

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.645

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

GnomAD4 genome AF: 0.627 AC: 95312 AN: 152098 Hom.: 32184 Cov.: 32 AF XY: 0.619 AC XY: 46004 AN XY: 74368

African (AFR) AF: 0.897 AC: 37246 AN: 41524

American (AMR) AF: 0.584 AC: 8922 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.625 AC: 2169 AN: 3470

East Asian (EAS) AF: 0.668 AC: 3460 AN: 5176

South Asian (SAS) AF: 0.617 AC: 2974 AN: 4822

European-Finnish (FIN) AF: 0.424 AC: 4474 AN: 10546

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.501 AC: 34067 AN: 67950

Other (OTH) AF: 0.641 AC: 1355 AN: 2114

Alfa AF: 0.566 Hom.: 3278

Bravo AF: 0.648

Asia WGS AF: 0.639 AC: 2224 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.0
DANN	Benign	0.84
PhyloP100		-0.72

Splicing

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

Other links and lift over

dbSNP: rs1333047; hg19: chr9-22124504; COSMIC: COSV69592465;