rs573687

Variant names:

• chr9-22011643-G-A
• rs573687
• ENST00000428597.7:n.371+16482G>A

Variant summary

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

The ENST00000428597.7(CDKN2B-AS1):​n.371+16482G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,000 control chromosomes in the GnomAD database, including 6,426 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 0.25 (6426 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.803
• Publications: 23 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=-0.69).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN2B-AS1	NR_003529.4	n.371+16482G>A		intron_variant	Intron 1 of 18	ENST00000428597.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000428597.7	n.371+16482G>A		intron_variant	Intron 1 of 18	1	NR_003529.4

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38693 AN: 151882 Hom.: 6419 Cov.: 32

Gnomad AFR AF: 0.0657

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.236

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

GnomAD4 genome AF: 0.255 AC: 38701 AN: 152000 Hom.: 6426 Cov.: 32 AF XY: 0.255 AC XY: 18944 AN XY: 74292

African (AFR) AF: 0.0656 AC: 2719 AN: 41474

American (AMR) AF: 0.185 AC: 2833 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 871 AN: 3466

East Asian (EAS) AF: 0.110 AC: 572 AN: 5182

South Asian (SAS) AF: 0.235 AC: 1130 AN: 4816

European-Finnish (FIN) AF: 0.399 AC: 4196 AN: 10506

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.374 AC: 25416 AN: 67964

Other (OTH) AF: 0.242 AC: 511 AN: 2112

Alfa AF: 0.315 Hom.: 9732

Bravo AF: 0.230

Asia WGS AF: 0.200 AC: 698 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	8.7
DANN	Benign	0.60
PhyloP100		0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs573687; hg19: chr9-22011642;