rs17694933

Variant names:

• chr9-22164310-G-A
• rs17694933
• ENST00000755351.1:n.302+36908G>A

Variant summary

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

The ENST00000755351.1(CDKN2B-AS1):​n.302+36908G>A 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 151,654 control chromosomes in the GnomAD database, including 19,465 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 (19465 hom., cov: 30)
• Consequence: CDKN2B-AS1 ENST00000755351.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00200
• Publications: 7 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]

ENSG00000298449 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000755351.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN2B-AS1	ENST00000755351.1		n.302+36908G>A		intron	N/A
	ENSG00000298449	ENST00000755556.1		n.169+1712C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.494 AC: 74788 AN: 151540 Hom.: 19436 Cov.: 30

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.643

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.437

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

GnomAD4 genome AF: 0.494 AC: 74868 AN: 151654 Hom.: 19465 Cov.: 30 AF XY: 0.496 AC XY: 36717 AN XY: 74038

African (AFR) AF: 0.651 AC: 26929 AN: 41374

American (AMR) AF: 0.497 AC: 7573 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1191 AN: 3470

East Asian (EAS) AF: 0.352 AC: 1810 AN: 5146

South Asian (SAS) AF: 0.645 AC: 3073 AN: 4768

European-Finnish (FIN) AF: 0.416 AC: 4359 AN: 10486

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.423 AC: 28729 AN: 67864

Other (OTH) AF: 0.439 AC: 920 AN: 2098

Alfa AF: 0.449 Hom.: 15624

Bravo AF: 0.500

Asia WGS AF: 0.565 AC: 1959 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.7
DANN	Benign	0.79
PhyloP100		0.0020

Splicing

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

Other links and lift over

dbSNP: rs17694933; hg19: chr9-22164309; COSMIC: COSV69451197;