9-22130516-G-A

Variant names:

• chr9-22130516-G-A
• rs10965245
• ENST00000755351.1:n.302+3114G>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+3114G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 151,996 control chromosomes in the GnomAD database, including 1,549 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 (1549 hom., cov: 33)
• Consequence: CDKN2B-AS1 ENST00000755351.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0700
• Publications: 21 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=-0.81).
• 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+3114G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19033 AN: 151878 Hom.: 1544 Cov.: 33

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.0522

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.0987

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0848

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.125 AC: 19059 AN: 151996 Hom.: 1549 Cov.: 33 AF XY: 0.127 AC XY: 9461 AN XY: 74284

African (AFR) AF: 0.182 AC: 7549 AN: 41432

American (AMR) AF: 0.107 AC: 1628 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0522 AC: 181 AN: 3470

East Asian (EAS) AF: 0.381 AC: 1963 AN: 5154

South Asian (SAS) AF: 0.122 AC: 587 AN: 4820

European-Finnish (FIN) AF: 0.0987 AC: 1040 AN: 10542

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

European-Non Finnish (NFE) AF: 0.0847 AC: 5759 AN: 67988

Other (OTH) AF: 0.115 AC: 243 AN: 2108

Alfa AF: 0.106 Hom.: 2152

Bravo AF: 0.131

Asia WGS AF: 0.246 AC: 855 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.1
DANN	Benign	0.46
PhyloP100		-0.070

Splicing

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

Other links and lift over

dbSNP: rs10965245; hg19: chr9-22130515;