rs10757279

chr9-22124631-A-Gchr9-22124631-A-T

Variant summary

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

The ENST00000650946.1(CDKN2B-AS1):n.439-2472A>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 0.406 in 152,060 control chromosomes in the GnomAD database, including 13,850 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 0.41 (13850 hom., cov: 33)
• Consequence: CDKN2B-AS1 ENST00000650946.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.337

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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDKN2B-AS1	ENST00000650946.1	n.439-2472A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61754 AN: 151942 Hom.: 13856 Cov.: 33

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.494

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.472

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

GnomAD4 genome AF: 0.406 AC: 61761 AN: 152060 Hom.: 13850 Cov.: 33 AF XY: 0.404 AC XY: 30005 AN XY: 74348

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.480

Gnomad4 ASJ AF: 0.586

Gnomad4 EAS AF: 0.508

Gnomad4 SAS AF: 0.526

Gnomad4 FIN AF: 0.417

Gnomad4 NFE AF: 0.487

Gnomad4 OTH AF: 0.468

Alfa AF: 0.452 Hom.: 3930

Bravo AF: 0.399

Asia WGS AF: 0.495 AC: 1723 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	3.4
Dann	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10757279; hg19: chr9-22124630; COSMIC: COSV69592467;