rs643319

Variant names:

• chr9-22017837-C-A
• rs643319
• ENST00000428597.7:n.372-11596C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-22017837-C-A
• chr9-22017837-C-G

Variant summary

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

The ENST00000428597.7(CDKN2B-AS1):​n.372-11596C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 152,002 control chromosomes in the GnomAD database, including 12,672 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 0.40 (12672 hom., cov: 33)
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.743
• Publications: 19 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN2B-AS1	NR_003529.4	n.372-11596C>A		intron_variant	Intron 1 of 18	ENST00000428597.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000428597.7	n.372-11596C>A		intron_variant	Intron 1 of 18	1	NR_003529.4

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60154 AN: 151884 Hom.: 12663 Cov.: 33

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.489

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.364

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

GnomAD4 genome AF: 0.396 AC: 60196 AN: 152002 Hom.: 12672 Cov.: 33 AF XY: 0.395 AC XY: 29356 AN XY: 74296

African (AFR) AF: 0.290 AC: 12029 AN: 41440

American (AMR) AF: 0.284 AC: 4344 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 1248 AN: 3468

East Asian (EAS) AF: 0.325 AC: 1683 AN: 5172

South Asian (SAS) AF: 0.347 AC: 1669 AN: 4812

European-Finnish (FIN) AF: 0.489 AC: 5165 AN: 10558

Middle Eastern (MID) AF: 0.298 AC: 87 AN: 292

European-Non Finnish (NFE) AF: 0.482 AC: 32777 AN: 67952

Other (OTH) AF: 0.370 AC: 782 AN: 2116

Alfa AF: 0.440 Hom.: 11618

Bravo AF: 0.374

Asia WGS AF: 0.337 AC: 1175 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	5.0
DANN	Benign	0.68
PhyloP100		0.74

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: rs643319; hg19: chr9-22017836;