chr9-22130390-A-T

Variant names:

• chr9-22130390-A-T
• rs10965244
• ENST00000755351.1:n.302+2988A>T

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+2988A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,244 control chromosomes in the GnomAD database, including 2,821 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 0.18 (2821 hom., cov: 33)
• Consequence: CDKN2B-AS1 ENST00000755351.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.254
• Publications: 8 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.224 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+2988A>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27451 AN: 152124 Hom.: 2822 Cov.: 33

Gnomad AFR AF: 0.0962

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.180 AC: 27463 AN: 152244 Hom.: 2821 Cov.: 33 AF XY: 0.179 AC XY: 13353 AN XY: 74428

African (AFR) AF: 0.0963 AC: 4003 AN: 41550

American (AMR) AF: 0.143 AC: 2188 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 786 AN: 3472

East Asian (EAS) AF: 0.113 AC: 584 AN: 5184

South Asian (SAS) AF: 0.153 AC: 736 AN: 4826

European-Finnish (FIN) AF: 0.292 AC: 3088 AN: 10588

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15469 AN: 68006

Other (OTH) AF: 0.186 AC: 394 AN: 2114

Alfa AF: 0.204 Hom.: 489

Bravo AF: 0.168

Asia WGS AF: 0.122 AC: 425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.1
DANN	Benign	0.33
PhyloP100		0.25

Splicing

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

Other links and lift over

dbSNP: rs10965244; hg19: chr9-22130389;