chr9-22029548-T-A

Variant names:

• chr9-22029548-T-A
• rs564398
• ENST00000428597.7:n.487T>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000428597.7(CDKN2B-AS1):​n.487T>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CDKN2B-AS1 ENST00000428597.7 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.156
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.487T>A		non_coding_transcript_exon	Exon 2 of 19
	CDKN2B-AS1	NR_047532.2		n.487T>A		non_coding_transcript_exon	Exon 2 of 14
	CDKN2B-AS1	NR_047539.2		n.487T>A		non_coding_transcript_exon	Exon 2 of 13

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.487T>A		non_coding_transcript_exon	Exon 2 of 19
	CDKN2B-AS1	ENST00000580576.6	TSL:1	n.487T>A		non_coding_transcript_exon	Exon 2 of 14
	CDKN2B-AS1	ENST00000584351.5	TSL:1	n.487T>A		non_coding_transcript_exon	Exon 2 of 13

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 626750 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 341500

African (AFR) AF: 0.00 AC: 0 AN: 17674

American (AMR) AF: 0.00 AC: 0 AN: 43700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20956

East Asian (EAS) AF: 0.00 AC: 0 AN: 36046

South Asian (SAS) AF: 0.00 AC: 0 AN: 69704

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51934

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4146

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 349568

Other (OTH) AF: 0.00 AC: 0 AN: 33022

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.2
DANN	Benign	0.78
PhyloP100		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.22		Position offset: 1

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

Other links and lift over

dbSNP: rs564398; hg19: chr9-22029547;