9-22033390-C-T

Variant names:

• chr9-22033390-C-T
• rs1759417
• ENST00000428597.6:n.846+404C>T

Variant summary

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

The ENST00000468603.7(CDKN2B-AS1):​n.1245C>T 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 0.0666 in 152,178 control chromosomes in the GnomAD database, including 456 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 0.067 (456 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000468603.7 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.469

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0978 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN2B-AS1	NR_003529.4	n.846+404C>T		intron_variant	Intron 3 of 18
CDKN2B-AS1	NR_047532.2	n.533+3796C>T		intron_variant	Intron 2 of 13
CDKN2B-AS1	NR_047533.2	n.372-13361C>T		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000428597.6	n.846+404C>T		intron_variant	Intron 3 of 18	1
CDKN2B-AS1	ENST00000455933.7	n.341-13361C>T		intron_variant	Intron 1 of 4	1
CDKN2B-AS1	ENST00000577551.5	n.261-13361C>T		intron_variant	Intron 1 of 6	1

Frequencies

GnomAD3 genomes AF: 0.0667 AC: 10136 AN: 152060 Hom.: 456 Cov.: 32

Gnomad AFR AF: 0.0181

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.0580

Gnomad ASJ AF: 0.0954

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.0298

Gnomad FIN AF: 0.0784

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0999

Gnomad OTH AF: 0.0779

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

GnomAD4 genome AF: 0.0666 AC: 10138 AN: 152178 Hom.: 456 Cov.: 32 AF XY: 0.0651 AC XY: 4844 AN XY: 74392

Gnomad4 AFR AF: 0.0181

Gnomad4 AMR AF: 0.0580

Gnomad4 ASJ AF: 0.0954

Gnomad4 EAS AF: 0.000581

Gnomad4 SAS AF: 0.0300

Gnomad4 FIN AF: 0.0784

Gnomad4 NFE AF: 0.0998

Gnomad4 OTH AF: 0.0785

Alfa AF: 0.0764 Hom.: 243

Bravo AF: 0.0643

Asia WGS AF: 0.0310 AC: 107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.96
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1759417; hg19: chr9-22033389;