9-22128601-G-A

Variant names:

• chr9-22128601-G-A
• rs10811658
• ENST00000755351.1:n.302+1199G>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+1199G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 151,960 control chromosomes in the GnomAD database, including 9,651 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 0.35 (9651 hom., cov: 31)
• Consequence: CDKN2B-AS1 ENST00000755351.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.751
• Publications: 10 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.473 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+1199G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52662 AN: 151842 Hom.: 9628 Cov.: 31

Gnomad AFR AF: 0.447

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.347 AC: 52741 AN: 151960 Hom.: 9651 Cov.: 31 AF XY: 0.346 AC XY: 25691 AN XY: 74266

African (AFR) AF: 0.448 AC: 18550 AN: 41424

American (AMR) AF: 0.272 AC: 4156 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 949 AN: 3468

East Asian (EAS) AF: 0.489 AC: 2512 AN: 5138

South Asian (SAS) AF: 0.270 AC: 1298 AN: 4806

European-Finnish (FIN) AF: 0.357 AC: 3767 AN: 10556

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.302 AC: 20495 AN: 67964

Other (OTH) AF: 0.329 AC: 695 AN: 2112

Alfa AF: 0.303 Hom.: 11258

Bravo AF: 0.349

Asia WGS AF: 0.396 AC: 1377 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.16
DANN	Benign	0.46
PhyloP100		-0.75

Splicing

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

Other links and lift over

dbSNP: rs10811658; hg19: chr9-22128600;