rs2383206

Variant names:

• chr9-22115027-A-G
• rs2383206
• ENST00000428597.7:n.2908+1228A>G

Variant summary

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

The ENST00000422420.3(CDKN2B-AS1):​n.299+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 ENST00000422420.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.53
• Publications: 177 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000422420.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN2B-AS1	NR_003529.4	MANE Select	n.2908+1228A>G		intron	N/A
	CDKN2B-AS1	NR_047532.2		n.1697+1228A>G		intron	N/A
	CDKN2B-AS1	NR_047534.2		n.961+1228A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.2908+1228A>G		intron	N/A
	CDKN2B-AS1	ENST00000422420.3	TSL:1	n.299+1228A>G		intron	N/A
	CDKN2B-AS1	ENST00000577551.5	TSL:1	n.609+2632A>G		intron	N/A

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

African (AFR) AF: 0.424 AC: 17564 AN: 41430

American (AMR) AF: 0.553 AC: 8438 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.663 AC: 2303 AN: 3472

East Asian (EAS) AF: 0.490 AC: 2532 AN: 5166

South Asian (SAS) AF: 0.553 AC: 2659 AN: 4804

European-Finnish (FIN) AF: 0.432 AC: 4556 AN: 10542

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.521 AC: 35379 AN: 67938

Other (OTH) AF: 0.554 AC: 1164 AN: 2102

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.024
DANN	Benign	0.47
PhyloP100		-2.5

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2383206;

hg19: chr9-22115026;

COSMIC: COSV69592433;