9-22136490-A-T

Variant names:

• chr9-22136490-A-T
• rs1333051
• ENST00000755351.1:n.302+9088A>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+9088A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,240 control chromosomes in the GnomAD database, including 1,238 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 0.12 (1238 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000755351.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.23
• 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=-0.58).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000755351.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN2B-AS1	ENST00000755351.1		n.302+9088A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18590 AN: 152122 Hom.: 1235 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.0895

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.122 AC: 18603 AN: 152240 Hom.: 1238 Cov.: 32 AF XY: 0.121 AC XY: 9006 AN XY: 74432

African (AFR) AF: 0.101 AC: 4216 AN: 41546

American (AMR) AF: 0.133 AC: 2031 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 439 AN: 3466

East Asian (EAS) AF: 0.143 AC: 740 AN: 5186

South Asian (SAS) AF: 0.0889 AC: 429 AN: 4824

European-Finnish (FIN) AF: 0.116 AC: 1224 AN: 10596

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9090 AN: 68006

Other (OTH) AF: 0.135 AC: 286 AN: 2116

Alfa AF: 0.121 Hom.: 697

Bravo AF: 0.123

Asia WGS AF: 0.127 AC: 442 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	19
DANN	Benign	0.79
PhyloP100		2.2

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1333051;

hg19: chr9-22136489;