9-22012423-G-C

Variant names:

• chr9-22012423-G-C
• rs545226
• ENST00000428597.7:n.372-17010G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000428597.7(CDKN2B-AS1):​n.372-17010G>C variant causes a intron 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: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46
• Publications: 19 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]

UBA52P6 (HGNC:36763): (ubiquitin A-52 residue ribosomal protein fusion product 1 pseudogene 6)

ENSG00000264545 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBA52P6		n.22012423G>C		intragenic_variant
CDKN2B-AS1	NR_003529.4	n.372-17010G>C		intron_variant	Intron 1 of 18
CDKN2B-AS1	NR_047532.2	n.372-17010G>C		intron_variant	Intron 1 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000428597.7	n.372-17010G>C		intron_variant	Intron 1 of 18	1
CDKN2B-AS1	ENST00000455933.8	n.340+17262G>C		intron_variant	Intron 1 of 4	1
CDKN2B-AS1	ENST00000577551.5	n.260+17262G>C		intron_variant	Intron 1 of 6	1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 594130 Hom.: 0 Cov.: 6 AF XY: 0.00 AC XY: 0 AN XY: 323570

African (AFR) AF: 0.00 AC: 0 AN: 16756

American (AMR) AF: 0.00 AC: 0 AN: 40284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19238

East Asian (EAS) AF: 0.00 AC: 0 AN: 33480

South Asian (SAS) AF: 0.00 AC: 0 AN: 67888

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42978

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2486

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 340554

Other (OTH) AF: 0.00 AC: 0 AN: 30466

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 73857

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.33
DANN	Benign	0.27
PhyloP100		1.5

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs545226; hg19: chr9-22012422;