9-22064466-A-G

Variant names:

• chr9-22064466-A-G
• rs8181047
• ENST00000428597.7:n.2233+448A>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.2233+448A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.79 in 152,030 control chromosomes in the GnomAD database, including 48,406 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 0.79 (48406 hom., cov: 31)
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.124
• Publications: 38 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN2B-AS1	NR_003529.4	n.2233+448A>G		intron_variant	Intron 10 of 18
CDKN2B-AS1	NR_047532.2	n.1075+8079A>G		intron_variant	Intron 6 of 13
CDKN2B-AS1	NR_047533.2	n.645-13213A>G		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000428597.7	n.2233+448A>G		intron_variant	Intron 10 of 18	1
CDKN2B-AS1	ENST00000455933.8	n.749+8079A>G		intron_variant	Intron 4 of 4	1
CDKN2B-AS1	ENST00000577551.5	n.533+15238A>G		intron_variant	Intron 3 of 6	1

Frequencies

GnomAD3 genomes AF: 0.789 AC: 119928 AN: 151912 Hom.: 48346 Cov.: 31

Gnomad AFR AF: 0.947

Gnomad AMI AF: 0.793

Gnomad AMR AF: 0.845

Gnomad ASJ AF: 0.812

Gnomad EAS AF: 0.873

Gnomad SAS AF: 0.788

Gnomad FIN AF: 0.651

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.817

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

GnomAD4 genome AF: 0.790 AC: 120042 AN: 152030 Hom.: 48406 Cov.: 31 AF XY: 0.787 AC XY: 58495 AN XY: 74286

African (AFR) AF: 0.948 AC: 39306 AN: 41482

American (AMR) AF: 0.845 AC: 12920 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.812 AC: 2815 AN: 3466

East Asian (EAS) AF: 0.873 AC: 4514 AN: 5170

South Asian (SAS) AF: 0.789 AC: 3802 AN: 4820

European-Finnish (FIN) AF: 0.651 AC: 6864 AN: 10548

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.694 AC: 47125 AN: 67946

Other (OTH) AF: 0.813 AC: 1713 AN: 2108

Alfa AF: 0.753 Hom.: 24476

Bravo AF: 0.812

Asia WGS AF: 0.821 AC: 2854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.5
DANN	Benign	0.78
PhyloP100		-0.12

Splicing

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

Other links and lift over

dbSNP: rs8181047; hg19: chr9-22064465;