9-22133985-T-C

Variant names:

• chr9-22133985-T-C
• rs10757282
• ENST00000755351.1:n.302+6583T>C

Variant summary

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

The ENST00000755351.1(CDKN2B-AS1):​n.302+6583T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 152,094 control chromosomes in the GnomAD database, including 12,218 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 0.39 (12218 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000755351.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.391
• Publications: 30 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000755351.1	n.302+6583T>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59250 AN: 151976 Hom.: 12215 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.430

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

GnomAD4 genome AF: 0.390 AC: 59261 AN: 152094 Hom.: 12218 Cov.: 32 AF XY: 0.394 AC XY: 29274 AN XY: 74340

African (AFR) AF: 0.256 AC: 10622 AN: 41526

American (AMR) AF: 0.405 AC: 6201 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1581 AN: 3470

East Asian (EAS) AF: 0.621 AC: 3206 AN: 5164

South Asian (SAS) AF: 0.441 AC: 2119 AN: 4810

European-Finnish (FIN) AF: 0.470 AC: 4955 AN: 10546

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.428 AC: 29113 AN: 67978

Other (OTH) AF: 0.430 AC: 907 AN: 2108

Alfa AF: 0.423 Hom.: 55943

Bravo AF: 0.381

Asia WGS AF: 0.529 AC: 1840 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.73
DANN	Benign	0.57
PhyloP100		-0.39

Splicing

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

Other links and lift over

dbSNP: rs10757282; hg19: chr9-22133984; COSMIC: COSV60341842;