rs7018475

Variant names:

• chr9-22137686-T-G
• rs7018475
• ENST00000755351.1:n.302+10284T>G

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+10284T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,018 control chromosomes in the GnomAD database, including 5,690 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 0.27 (5690 hom., cov: 31)
• Consequence: CDKN2B-AS1 ENST00000755351.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.91
• Publications: 45 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.356 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+10284T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41565 AN: 151898 Hom.: 5687 Cov.: 31

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.299

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

GnomAD4 genome AF: 0.274 AC: 41577 AN: 152018 Hom.: 5690 Cov.: 31 AF XY: 0.275 AC XY: 20407 AN XY: 74308

African (AFR) AF: 0.262 AC: 10843 AN: 41452

American (AMR) AF: 0.272 AC: 4156 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1046 AN: 3470

East Asian (EAS) AF: 0.370 AC: 1902 AN: 5144

South Asian (SAS) AF: 0.339 AC: 1630 AN: 4812

European-Finnish (FIN) AF: 0.267 AC: 2824 AN: 10566

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.267 AC: 18130 AN: 67976

Other (OTH) AF: 0.297 AC: 627 AN: 2108

Alfa AF: 0.273 Hom.: 22649

Bravo AF: 0.274

Asia WGS AF: 0.339 AC: 1184 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	16
DANN	Benign	0.41
PhyloP100		2.9

Splicing

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

Other links and lift over

dbSNP: rs7018475; hg19: chr9-22137685;