chr9-22087474-T-C

Position:

• chr9-22087474-T-C

Variant summary

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

The NR_003529.3(CDKN2B-AS1):​n.2449-8898T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.79 in 152,190 control chromosomes in the GnomAD database, including 48,439 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 0.79 (48439 hom., cov: 32)
• Consequence: CDKN2B-AS1 NR_003529.3 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.311

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDKN2B-AS1	NR_003529.3	n.2449-8898T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000650946.1	n.438+31087T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.790 AC: 120118 AN: 152072 Hom.: 48377 Cov.: 32

Gnomad AFR AF: 0.942

Gnomad AMI AF: 0.769

Gnomad AMR AF: 0.863

Gnomad ASJ AF: 0.819

Gnomad EAS AF: 0.680

Gnomad SAS AF: 0.776

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.712

Gnomad OTH AF: 0.822

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

GnomAD4 genome AF: 0.790 AC: 120239 AN: 152190 Hom.: 48439 Cov.: 32 AF XY: 0.786 AC XY: 58449 AN XY: 74404

Gnomad4 AFR AF: 0.942

Gnomad4 AMR AF: 0.863

Gnomad4 ASJ AF: 0.819

Gnomad4 EAS AF: 0.681

Gnomad4 SAS AF: 0.777

Gnomad4 FIN AF: 0.634

Gnomad4 NFE AF: 0.712

Gnomad4 OTH AF: 0.818

Alfa AF: 0.743 Hom.: 11554

Bravo AF: 0.813

Asia WGS AF: 0.736 AC: 2559 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.4
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: rs7857345; hg19: chr9-22087473;