ENST00000422420.2:n.135-1004T>C

Variant names:

• chr9-22119196-T-C
• rs1333045
• ENST00000422420.2:n.135-1004T>C

Variant summary

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

The ENST00000422420.2(CDKN2B-AS1):​n.135-1004T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 151,756 control chromosomes in the GnomAD database, including 19,474 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 0.51 (19474 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: CDKN2B-AS1 ENST00000422420.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.249

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN2B-AS1	NR_003529.4	n.3032+429T>C		intron_variant	Intron 17 of 18
CDKN2B-AS1	NR_047532.2	n.1821+429T>C		intron_variant	Intron 12 of 13
CDKN2B-AS1	NR_047534.2	n.1085+429T>C		intron_variant	Intron 7 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000422420.2	n.135-1004T>C		intron_variant	Intron 1 of 2	1
CDKN2B-AS1	ENST00000428597.6	n.3032+429T>C		intron_variant	Intron 17 of 18	1
CDKN2B-AS1	ENST00000577551.5	n.733+429T>C		intron_variant	Intron 5 of 6	1

Frequencies

GnomAD3 genomes AF: 0.507 AC: 76872 AN: 151638 Hom.: 19462 Cov.: 31

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.555

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

GnomAD4 genome AF: 0.507 AC: 76912 AN: 151756 Hom.: 19474 Cov.: 31 AF XY: 0.501 AC XY: 37128 AN XY: 74132

Gnomad4 AFR AF: 0.471

Gnomad4 AMR AF: 0.526

Gnomad4 ASJ AF: 0.614

Gnomad4 EAS AF: 0.519

Gnomad4 SAS AF: 0.541

Gnomad4 FIN AF: 0.458

Gnomad4 NFE AF: 0.521

Gnomad4 OTH AF: 0.549

Alfa AF: 0.511 Hom.: 5537

Bravo AF: 0.508

Asia WGS AF: 0.521 AC: 1814 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.7
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1333045; hg19: chr9-22119195;