rs3218009

Variant names:

• chr9-21998758-C-G
• rs3218009
• ENST00000428597.7:n.371+3597C>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.371+3597C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0783 in 152,178 control chromosomes in the GnomAD database, including 661 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 0.078 (661 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60
• Publications: 26 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]

ENSG00000264545 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000428597.7. 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.371+3597C>G		intron	N/A
	CDKN2B-AS1	NR_047532.2		n.371+3597C>G		intron	N/A
	CDKN2B-AS1	NR_047533.2		n.371+3597C>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.371+3597C>G		intron	N/A
	CDKN2B-AS1	ENST00000455933.8	TSL:1	n.340+3597C>G		intron	N/A
	CDKN2B-AS1	ENST00000577551.5	TSL:1	n.260+3597C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0784 AC: 11915 AN: 152060 Hom.: 661 Cov.: 32

Gnomad AFR AF: 0.0204

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0466

Gnomad ASJ AF: 0.0395

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0101

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.0535

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

GnomAD4 genome AF: 0.0783 AC: 11914 AN: 152178 Hom.: 661 Cov.: 32 AF XY: 0.0769 AC XY: 5723 AN XY: 74402

African (AFR) AF: 0.0203 AC: 844 AN: 41534

American (AMR) AF: 0.0466 AC: 712 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0395 AC: 137 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.0102 AC: 49 AN: 4824

European-Finnish (FIN) AF: 0.136 AC: 1443 AN: 10572

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8546 AN: 67976

Other (OTH) AF: 0.0530 AC: 112 AN: 2114

Alfa AF: 0.108 Hom.: 132

Bravo AF: 0.0685

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.48
DANN	Benign	0.82
PhyloP100		-1.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs3218009; hg19: chr9-21998757;