rs2891168

Variant names:

• chr9-22098620-A-G
• rs2891168
• ENST00000428597.7:n.2698+1256A>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.2698+1256A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 152,066 control chromosomes in the GnomAD database, including 14,116 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 0.41 (14116 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.442
• Publications: 119 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN2B-AS1	NR_003529.4	n.2698+1256A>G		intron_variant	Intron 14 of 18	ENST00000428597.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000428597.7	n.2698+1256A>G		intron_variant	Intron 14 of 18	1	NR_003529.4

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62341 AN: 151948 Hom.: 14129 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.495

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.480

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

GnomAD4 genome AF: 0.410 AC: 62343 AN: 152066 Hom.: 14116 Cov.: 32 AF XY: 0.407 AC XY: 30283 AN XY: 74350

African (AFR) AF: 0.201 AC: 8330 AN: 41514

American (AMR) AF: 0.453 AC: 6912 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.621 AC: 2151 AN: 3466

East Asian (EAS) AF: 0.486 AC: 2508 AN: 5156

South Asian (SAS) AF: 0.523 AC: 2520 AN: 4816

European-Finnish (FIN) AF: 0.433 AC: 4581 AN: 10568

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.496 AC: 33696 AN: 67972

Other (OTH) AF: 0.476 AC: 1007 AN: 2116

Alfa AF: 0.465 Hom.: 26172

Bravo AF: 0.400

Asia WGS AF: 0.492 AC: 1709 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.42
DANN	Benign	0.68
PhyloP100		-0.44

Splicing

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

Other links and lift over

dbSNP: rs2891168; hg19: chr9-22098619;