rs495490

Positions:

• chr9-22010413-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_003529.3(CDKN2B-AS1):​n.371+15252A>G variant causes a intron, non coding transcript 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 NR_003529.3 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.130

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDKN2B-AS1	NR_003529.3	n.371+15252A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000650946.1	n.29+15252A>G		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.0181

Gnomad4 AMR AF: 0.0580

Gnomad4 ASJ AF: 0.0933

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0325

Gnomad4 FIN AF: 0.0762

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.0799

Alfa AF: 0.0839 Hom.: 158

Bravo AF: 0.0648

Asia WGS AF: 0.0350 AC: 121 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs495490; hg19: chr9-22010412;