rs1537371

Variant names:

• chr9-22099569-C-A
• rs1537371
• ENST00000428597.7:n.2698+2205C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-22099569-C-A
• chr9-22099569-C-G
• chr9-22099569-C-T

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+2205C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 151,894 control chromosomes in the GnomAD database, including 32,138 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 0.63 (32138 hom., cov: 31)
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.730
• Publications: 54 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=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN2B-AS1	NR_003529.4	n.2698+2205C>A		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+2205C>A		intron_variant	Intron 14 of 18	1	NR_003529.4

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95141 AN: 151776 Hom.: 32094 Cov.: 31

Gnomad AFR AF: 0.893

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.670

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.650

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

GnomAD4 genome AF: 0.627 AC: 95243 AN: 151894 Hom.: 32138 Cov.: 31 AF XY: 0.618 AC XY: 45881 AN XY: 74210

African (AFR) AF: 0.893 AC: 37019 AN: 41464

American (AMR) AF: 0.555 AC: 8456 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 2293 AN: 3468

East Asian (EAS) AF: 0.671 AC: 3464 AN: 5166

South Asian (SAS) AF: 0.618 AC: 2971 AN: 4810

European-Finnish (FIN) AF: 0.421 AC: 4419 AN: 10496

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.509 AC: 34586 AN: 67930

Other (OTH) AF: 0.646 AC: 1364 AN: 2112

Alfa AF: 0.574 Hom.: 13627

Bravo AF: 0.646

Asia WGS AF: 0.635 AC: 2205 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.5
DANN	Benign	0.81
PhyloP100		0.73

Splicing

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

Other links and lift over

dbSNP: rs1537371; hg19: chr9-22099568;