9-22049131-C-G

Position:

• chr9-22049131-C-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.1155C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 151,968 control chromosomes in the GnomAD database, including 19,024 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 0.49 (19024 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CDKN2B-AS1 NR_003529.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.585

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDKN2B-AS1	NR_003529.3	n.1155C>G		non_coding_transcript_exon_variant	6/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDKN2B-AS1	ENST00000650946.1	n.205C>G		non_coding_transcript_exon_variant	3/5

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74833 AN: 151850 Hom.: 19018 Cov.: 32

Gnomad AFR AF: 0.425

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.581

Gnomad EAS AF: 0.694

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.542

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.493 AC: 74863 AN: 151968 Hom.: 19024 Cov.: 32 AF XY: 0.498 AC XY: 36954 AN XY: 74266

Gnomad4 AFR AF: 0.424

Gnomad4 AMR AF: 0.654

Gnomad4 ASJ AF: 0.581

Gnomad4 EAS AF: 0.694

Gnomad4 SAS AF: 0.638

Gnomad4 FIN AF: 0.473

Gnomad4 NFE AF: 0.469

Gnomad4 OTH AF: 0.538

Alfa AF: 0.297 Hom.: 655

Bravo AF: 0.506

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.0
DANN	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10738605; hg19: chr9-22049130;