9-22131826-A-G

Variant names:

• chr9-22131826-A-G
• rs2891169
• ENST00000755351.1:n.302+4424A>G

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+4424A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 151,738 control chromosomes in the GnomAD database, including 14,252 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 0.43 (14252 hom., cov: 30)
• Consequence: CDKN2B-AS1 ENST00000755351.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.415
• Publications: 12 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000755351.1	n.302+4424A>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65199 AN: 151620 Hom.: 14234 Cov.: 30

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.571

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.440

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

GnomAD4 genome AF: 0.430 AC: 65251 AN: 151738 Hom.: 14252 Cov.: 30 AF XY: 0.432 AC XY: 32037 AN XY: 74126

African (AFR) AF: 0.488 AC: 20177 AN: 41356

American (AMR) AF: 0.406 AC: 6184 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1416 AN: 3464

East Asian (EAS) AF: 0.572 AC: 2935 AN: 5134

South Asian (SAS) AF: 0.474 AC: 2280 AN: 4812

European-Finnish (FIN) AF: 0.408 AC: 4295 AN: 10516

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.390 AC: 26449 AN: 67902

Other (OTH) AF: 0.440 AC: 927 AN: 2106

Alfa AF: 0.400 Hom.: 6957

Bravo AF: 0.434

Asia WGS AF: 0.534 AC: 1858 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.8
DANN	Benign	0.53
PhyloP100		-0.41

Splicing

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

Other links and lift over

dbSNP: rs2891169; hg19: chr9-22131825;