9-22124478-A-G

Variant names:

• chr9-22124478-A-G
• rs10757278
• ENST00000650946.1:n.439-2625A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000650946.1(CDKN2B-AS1):​n.439-2625A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 151,872 control chromosomes in the GnomAD database, including 13,708 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 0.40 (13708 hom., cov: 33)
• Consequence: CDKN2B-AS1 ENST00000650946.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0760
• Publications: 384 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=-0.75).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000650946.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN2B-AS1	NR_185859.1		n.781-2625A>G		intron	N/A
	CDKN2B-AS1	NR_185867.1		n.1256-2625A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN2B-AS1	ENST00000650946.1		n.439-2625A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61496 AN: 151754 Hom.: 13714 Cov.: 33

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.468

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

GnomAD4 genome AF: 0.405 AC: 61504 AN: 151872 Hom.: 13708 Cov.: 33 AF XY: 0.402 AC XY: 29839 AN XY: 74214

African (AFR) AF: 0.195 AC: 8113 AN: 41502

American (AMR) AF: 0.479 AC: 7312 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 2030 AN: 3464

East Asian (EAS) AF: 0.507 AC: 2616 AN: 5158

South Asian (SAS) AF: 0.525 AC: 2526 AN: 4808

European-Finnish (FIN) AF: 0.412 AC: 4335 AN: 10516

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.486 AC: 32998 AN: 67854

Other (OTH) AF: 0.463 AC: 972 AN: 2098

Alfa AF: 0.467 Hom.: 54815

Bravo AF: 0.399

Asia WGS AF: 0.495 AC: 1721 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	9.9
DANN	Benign	0.74
PhyloP100		0.076

Splicing

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

Other links and lift over

dbSNP: rs10757278; hg19: chr9-22124477; COSMIC: COSV69592462;