9-22115287-T-C

Variant names:

• chr9-22115287-T-C
• rs944797
• ENST00000428597.7:n.2908+1488T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000422420.3(CDKN2B-AS1):​n.299+1488T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 151,974 control chromosomes in the GnomAD database, including 18,827 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 0.49 (18827 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000422420.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.225
• Publications: 61 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000422420.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN2B-AS1	NR_003529.4	MANE Select	n.2908+1488T>C		intron	N/A
	CDKN2B-AS1	NR_047532.2		n.1697+1488T>C		intron	N/A
	CDKN2B-AS1	NR_047534.2		n.961+1488T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.2908+1488T>C		intron	N/A
	CDKN2B-AS1	ENST00000422420.3	TSL:1	n.299+1488T>C		intron	N/A
	CDKN2B-AS1	ENST00000577551.5	TSL:1	n.609+2892T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75114 AN: 151856 Hom.: 18833 Cov.: 32

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.488

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.556

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

GnomAD4 genome AF: 0.494 AC: 75137 AN: 151974 Hom.: 18827 Cov.: 32 AF XY: 0.490 AC XY: 36356 AN XY: 74254

African (AFR) AF: 0.422 AC: 17471 AN: 41448

American (AMR) AF: 0.553 AC: 8439 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.663 AC: 2303 AN: 3472

East Asian (EAS) AF: 0.488 AC: 2516 AN: 5156

South Asian (SAS) AF: 0.554 AC: 2663 AN: 4810

European-Finnish (FIN) AF: 0.431 AC: 4550 AN: 10552

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.521 AC: 35375 AN: 67954

Other (OTH) AF: 0.551 AC: 1164 AN: 2114

Alfa AF: 0.507 Hom.: 54191

Bravo AF: 0.496

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.7
DANN	Benign	0.68
PhyloP100		0.23

Splicing

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

Other links and lift over

dbSNP: rs944797; hg19: chr9-22115286; COSMIC: COSV69592437;