rs518394

Variant names:

• chr9-22019674-G-C
• rs518394
• ENST00000428597.7:n.372-9759G>C

Variant summary

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

The ENST00000428597.7(CDKN2B-AS1):​n.372-9759G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 152,002 control chromosomes in the GnomAD database, including 8,575 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 0.30 (8575 hom., cov: 31)
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07
• Publications: 42 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]

ENSG00000264545 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000428597.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN2B-AS1	NR_003529.4	MANE Select	n.372-9759G>C		intron	N/A
	CDKN2B-AS1	NR_047532.2		n.372-9759G>C		intron	N/A
	CDKN2B-AS1	NR_047533.2		n.371+24513G>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.372-9759G>C		intron	N/A
	CDKN2B-AS1	ENST00000455933.8	TSL:1	n.340+24513G>C		intron	N/A
	CDKN2B-AS1	ENST00000577551.5	TSL:1	n.260+24513G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44881 AN: 151884 Hom.: 8568 Cov.: 31

Gnomad AFR AF: 0.0762

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.295 AC: 44889 AN: 152002 Hom.: 8575 Cov.: 31 AF XY: 0.293 AC XY: 21800 AN XY: 74282

African (AFR) AF: 0.0761 AC: 3156 AN: 41496

American (AMR) AF: 0.226 AC: 3445 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1123 AN: 3466

East Asian (EAS) AF: 0.108 AC: 557 AN: 5168

South Asian (SAS) AF: 0.264 AC: 1271 AN: 4808

European-Finnish (FIN) AF: 0.432 AC: 4549 AN: 10530

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.437 AC: 29676 AN: 67952

Other (OTH) AF: 0.286 AC: 604 AN: 2112

Alfa AF: 0.376 Hom.: 1704

Bravo AF: 0.272

Asia WGS AF: 0.210 AC: 733 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.7
DANN	Benign	0.68
PhyloP100		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs518394; hg19: chr9-22019673;