rs12347779

Variant names:

• chr9-22128710-C-G
• rs12347779
• ENST00000755351.1:n.302+1308C>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+1308C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0579 in 152,194 control chromosomes in the GnomAD database, including 304 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 0.058 (304 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000755351.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.105
• Publications: 7 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0621 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+1308C>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.0580 AC: 8816 AN: 152076 Hom.: 304 Cov.: 32

Gnomad AFR AF: 0.0642

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.0507

Gnomad ASJ AF: 0.0576

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0182

Gnomad FIN AF: 0.0609

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0604

Gnomad OTH AF: 0.0608

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

GnomAD4 genome AF: 0.0579 AC: 8818 AN: 152194 Hom.: 304 Cov.: 32 AF XY: 0.0570 AC XY: 4240 AN XY: 74412

African (AFR) AF: 0.0641 AC: 2663 AN: 41532

American (AMR) AF: 0.0506 AC: 774 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0576 AC: 200 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.0180 AC: 87 AN: 4820

European-Finnish (FIN) AF: 0.0609 AC: 644 AN: 10582

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0604 AC: 4106 AN: 68004

Other (OTH) AF: 0.0602 AC: 127 AN: 2110

Alfa AF: 0.0636 Hom.: 43

Bravo AF: 0.0569

Asia WGS AF: 0.0120 AC: 44 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.1
DANN	Benign	0.40
PhyloP100		-0.10

Splicing

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

Other links and lift over

dbSNP: rs12347779; hg19: chr9-22128709;