rs1333037

Positions:

• chr9-22040766-C-T

Variant summary

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

The ENST00000428597.6(CDKN2B-AS1):​n.847-5551C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.715 in 151,902 control chromosomes in the GnomAD database, including 40,750 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 0.72 (40750 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000428597.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.53

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDKN2B-AS1	NR_003529.4	n.847-5551C>T		intron_variant
CDKN2B-AS1	NR_047532.2	n.534-5551C>T		intron_variant
CDKN2B-AS1	NR_047533.2	n.372-5985C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000428597.6	n.847-5551C>T		intron_variant		1
CDKN2B-AS1	ENST00000455933.7	n.341-5985C>T		intron_variant		1
CDKN2B-AS1	ENST00000577551.5	n.261-5985C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.715 AC: 108570 AN: 151784 Hom.: 40691 Cov.: 32

Gnomad AFR AF: 0.926

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.783

Gnomad ASJ AF: 0.720

Gnomad EAS AF: 0.890

Gnomad SAS AF: 0.754

Gnomad FIN AF: 0.579

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.734

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

GnomAD4 genome AF: 0.715 AC: 108682 AN: 151902 Hom.: 40750 Cov.: 32 AF XY: 0.716 AC XY: 53179 AN XY: 74228

Gnomad4 AFR AF: 0.927

Gnomad4 AMR AF: 0.783

Gnomad4 ASJ AF: 0.720

Gnomad4 EAS AF: 0.890

Gnomad4 SAS AF: 0.754

Gnomad4 FIN AF: 0.579

Gnomad4 NFE AF: 0.578

Gnomad4 OTH AF: 0.729

Alfa AF: 0.640 Hom.: 9364

Bravo AF: 0.739

Asia WGS AF: 0.796 AC: 2767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.0040
DANN	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1333037; hg19: chr9-22040765;