rs10965250

Variant names:

• chr9-22133285-G-A
• rs10965250
• ENST00000755351.1:n.302+5883G>A

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+5883G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,014 control chromosomes in the GnomAD database, including 2,029 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 0.15 (2029 hom., cov: 33)
• Consequence: CDKN2B-AS1 ENST00000755351.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.97
• Publications: 79 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.399 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+5883G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22174 AN: 151896 Hom.: 2030 Cov.: 33

Gnomad AFR AF: 0.0699

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.146 AC: 22172 AN: 152014 Hom.: 2029 Cov.: 33 AF XY: 0.147 AC XY: 10923 AN XY: 74282

African (AFR) AF: 0.0698 AC: 2892 AN: 41454

American (AMR) AF: 0.158 AC: 2421 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 556 AN: 3466

East Asian (EAS) AF: 0.413 AC: 2134 AN: 5162

South Asian (SAS) AF: 0.144 AC: 694 AN: 4818

European-Finnish (FIN) AF: 0.143 AC: 1514 AN: 10560

Middle Eastern (MID) AF: 0.205 AC: 60 AN: 292

European-Non Finnish (NFE) AF: 0.168 AC: 11435 AN: 67962

Other (OTH) AF: 0.161 AC: 340 AN: 2106

Alfa AF: 0.170 Hom.: 8498

Bravo AF: 0.146

Asia WGS AF: 0.292 AC: 1014 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	12
DANN	Benign	0.67
PhyloP100		2.0

Splicing

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

Other links and lift over

dbSNP: rs10965250; hg19: chr9-22133284;