9-22130066-A-G

Variant names:

• chr9-22130066-A-G
• rs10965243
• ENST00000755351.1:n.302+2664A>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+2664A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,234 control chromosomes in the GnomAD database, including 1,596 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 0.13 (1596 hom., cov: 33)
• Consequence: CDKN2B-AS1 ENST00000755351.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.402
• Publications: 12 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.367 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN2B-AS1	ENST00000755351.1		n.302+2664A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19532 AN: 152116 Hom.: 1591 Cov.: 33

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0557

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0888

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.128 AC: 19558 AN: 152234 Hom.: 1596 Cov.: 33 AF XY: 0.130 AC XY: 9710 AN XY: 74428

African (AFR) AF: 0.184 AC: 7620 AN: 41502

American (AMR) AF: 0.107 AC: 1645 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0557 AC: 193 AN: 3468

East Asian (EAS) AF: 0.381 AC: 1970 AN: 5164

South Asian (SAS) AF: 0.124 AC: 597 AN: 4830

European-Finnish (FIN) AF: 0.107 AC: 1139 AN: 10620

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0887 AC: 6035 AN: 68022

Other (OTH) AF: 0.118 AC: 250 AN: 2116

Alfa AF: 0.102 Hom.: 1504

Bravo AF: 0.134

Asia WGS AF: 0.246 AC: 857 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.3
DANN	Benign	0.56
PhyloP100		-0.40

Splicing

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

Other links and lift over

dbSNP: rs10965243; hg19: chr9-22130065;