9-22019130-A-G

Variant names:

• chr9-22019130-A-G
• rs523096
• ENST00000428597.7:n.372-10303A>G

Variant summary

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

The ENST00000428597.7(CDKN2B-AS1):​n.372-10303A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 152,174 control chromosomes in the GnomAD database, including 8,660 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 0.30 (8660 hom., cov: 33)
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.00
• Publications: 56 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]

ENSG00000264545 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000428597.7. 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_003529.4	MANE Select	n.372-10303A>G		intron	N/A
	CDKN2B-AS1	NR_047532.2		n.372-10303A>G		intron	N/A
	CDKN2B-AS1	NR_047533.2		n.371+23969A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.372-10303A>G		intron	N/A
	CDKN2B-AS1	ENST00000455933.8	TSL:1	n.340+23969A>G		intron	N/A
	CDKN2B-AS1	ENST00000577551.5	TSL:1	n.260+23969A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.296 AC: 45074 AN: 152056 Hom.: 8652 Cov.: 33

Gnomad AFR AF: 0.0766

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.296 AC: 45083 AN: 152174 Hom.: 8660 Cov.: 33 AF XY: 0.295 AC XY: 21916 AN XY: 74400

African (AFR) AF: 0.0764 AC: 3176 AN: 41546

American (AMR) AF: 0.226 AC: 3451 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 1129 AN: 3466

East Asian (EAS) AF: 0.109 AC: 566 AN: 5178

South Asian (SAS) AF: 0.265 AC: 1277 AN: 4822

European-Finnish (FIN) AF: 0.433 AC: 4579 AN: 10574

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.438 AC: 29786 AN: 67970

Other (OTH) AF: 0.287 AC: 607 AN: 2116

Alfa AF: 0.389 Hom.: 30883

Bravo AF: 0.273

Asia WGS AF: 0.217 AC: 755 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.8
DANN	Benign	0.64
PhyloP100		2.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs523096; hg19: chr9-22019129;