rs495490

Variant names:

• chr9-22010413-A-G
• rs495490
• ENST00000428597.7:n.371+15252A>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+15252A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0671 in 152,286 control chromosomes in the GnomAD database, including 463 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 0.067 (463 hom., cov: 33)
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.130
• Publications: 15 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0987 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN2B-AS1	NR_003529.4	MANE Select	n.371+15252A>G		intron	N/A
	CDKN2B-AS1	NR_047532.2		n.371+15252A>G		intron	N/A
	CDKN2B-AS1	NR_047533.2		n.371+15252A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.371+15252A>G		intron	N/A
	CDKN2B-AS1	ENST00000455933.8	TSL:1	n.340+15252A>G		intron	N/A
	CDKN2B-AS1	ENST00000577551.5	TSL:1	n.260+15252A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0671 AC: 10209 AN: 152168 Hom.: 462 Cov.: 33

Gnomad AFR AF: 0.0181

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.0581

Gnomad ASJ AF: 0.0933

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0323

Gnomad FIN AF: 0.0762

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.0789

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

GnomAD4 genome AF: 0.0671 AC: 10212 AN: 152286 Hom.: 463 Cov.: 33 AF XY: 0.0653 AC XY: 4859 AN XY: 74450

African (AFR) AF: 0.0181 AC: 751 AN: 41558

American (AMR) AF: 0.0580 AC: 888 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0933 AC: 324 AN: 3472

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5184

South Asian (SAS) AF: 0.0325 AC: 157 AN: 4828

European-Finnish (FIN) AF: 0.0762 AC: 808 AN: 10604

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6847 AN: 68022

Other (OTH) AF: 0.0799 AC: 169 AN: 2114

Alfa AF: 0.0885 Hom.: 323

Bravo AF: 0.0648

Asia WGS AF: 0.0350 AC: 121 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.1
DANN	Benign	0.70
PhyloP100		-0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs495490; hg19: chr9-22010412;