rs12352425

Variant names:

• chr9-22042087-G-A
• rs12352425
• ENST00000428597.7:n.847-4230G>A

Variant summary

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

The ENST00000428597.7(CDKN2B-AS1):​n.847-4230G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 151,944 control chromosomes in the GnomAD database, including 2,817 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 0.16 (2817 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.12
• Publications: 10 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=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN2B-AS1	NR_003529.4	n.847-4230G>A		intron_variant	Intron 3 of 18
CDKN2B-AS1	NR_047532.2	n.534-4230G>A		intron_variant	Intron 2 of 13
CDKN2B-AS1	NR_047533.2	n.372-4664G>A		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000428597.7	n.847-4230G>A		intron_variant	Intron 3 of 18	1
CDKN2B-AS1	ENST00000455933.8	n.341-4664G>A		intron_variant	Intron 1 of 4	1
CDKN2B-AS1	ENST00000577551.5	n.261-4664G>A		intron_variant	Intron 1 of 6	1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25035 AN: 151826 Hom.: 2815 Cov.: 32

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.0899

Gnomad EAS AF: 0.0883

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0866

Gnomad OTH AF: 0.141

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

GnomAD4 genome AF: 0.165 AC: 25060 AN: 151944 Hom.: 2817 Cov.: 32 AF XY: 0.168 AC XY: 12472 AN XY: 74264

African (AFR) AF: 0.285 AC: 11805 AN: 41450

American (AMR) AF: 0.271 AC: 4129 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.0899 AC: 311 AN: 3460

East Asian (EAS) AF: 0.0879 AC: 452 AN: 5142

South Asian (SAS) AF: 0.205 AC: 986 AN: 4814

European-Finnish (FIN) AF: 0.105 AC: 1113 AN: 10594

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0866 AC: 5880 AN: 67922

Other (OTH) AF: 0.141 AC: 297 AN: 2108

Alfa AF: 0.131 Hom.: 1113

Bravo AF: 0.184

Asia WGS AF: 0.175 AC: 607 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.084
DANN	Benign	0.75
PhyloP100		-2.1

Splicing

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

Other links and lift over

dbSNP: rs12352425; hg19: chr9-22042086;