rs2383206

Variant names:

• chr9-22115027-A-G
• rs2383206
• ENST00000422420.2:n.134+1228A>G

Variant summary

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

The ENST00000422420.2(CDKN2B-AS1):​n.134+1228A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 151,922 control chromosomes in the GnomAD database, including 18,894 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 0.50 (18894 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000422420.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.53

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN2B-AS1	NR_003529.4	n.2908+1228A>G		intron_variant	Intron 16 of 18
CDKN2B-AS1	NR_047532.2	n.1697+1228A>G		intron_variant	Intron 11 of 13
CDKN2B-AS1	NR_047534.2	n.961+1228A>G		intron_variant	Intron 6 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000422420.2	n.134+1228A>G		intron_variant	Intron 1 of 2	1
CDKN2B-AS1	ENST00000428597.6	n.2908+1228A>G		intron_variant	Intron 16 of 18	1
CDKN2B-AS1	ENST00000577551.5	n.609+2632A>G		intron_variant	Intron 4 of 6	1

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75225 AN: 151804 Hom.: 18897 Cov.: 32

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.560

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

GnomAD4 genome AF: 0.495 AC: 75253 AN: 151922 Hom.: 18894 Cov.: 32 AF XY: 0.491 AC XY: 36427 AN XY: 74222

Gnomad4 AFR AF: 0.424 AC: 0.423944 AN: 0.423944

Gnomad4 AMR AF: 0.553 AC: 0.552659 AN: 0.552659

Gnomad4 ASJ AF: 0.663 AC: 0.663306 AN: 0.663306

Gnomad4 EAS AF: 0.490 AC: 0.490128 AN: 0.490128

Gnomad4 SAS AF: 0.553 AC: 0.553497 AN: 0.553497

Gnomad4 FIN AF: 0.432 AC: 0.432176 AN: 0.432176

Gnomad4 NFE AF: 0.521 AC: 0.520754 AN: 0.520754

Gnomad4 OTH AF: 0.554 AC: 0.553758 AN: 0.553758

Alfa AF: 0.514 Hom.: 33781

Bravo AF: 0.497

Asia WGS AF: 0.520 AC: 1810 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.024
DANN	Benign	0.47

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2383206; hg19: chr9-22115026; COSMIC: COSV69592433;