9-22134303-C-G

Variant names:

• chr9-22134303-C-G
• rs7019437
• ENST00000755351.1:n.302+6901C>G

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+6901C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 151,988 control chromosomes in the GnomAD database, including 11,822 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 0.38 (11822 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000755351.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.604 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN2B-AS1	ENST00000755351.1		n.302+6901C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58404 AN: 151870 Hom.: 11821 Cov.: 32

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.424

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

GnomAD4 genome AF: 0.384 AC: 58412 AN: 151988 Hom.: 11822 Cov.: 32 AF XY: 0.388 AC XY: 28822 AN XY: 74274

African (AFR) AF: 0.257 AC: 10662 AN: 41468

American (AMR) AF: 0.405 AC: 6183 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 1535 AN: 3468

East Asian (EAS) AF: 0.622 AC: 3206 AN: 5156

South Asian (SAS) AF: 0.473 AC: 2280 AN: 4820

European-Finnish (FIN) AF: 0.433 AC: 4563 AN: 10534

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.420 AC: 28527 AN: 67960

Other (OTH) AF: 0.425 AC: 896 AN: 2110

Alfa AF: 0.399 Hom.: 1514

Bravo AF: 0.377

Asia WGS AF: 0.540 AC: 1877 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.60
DANN	Benign	0.58
PhyloP100		-1.8

Splicing

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

Other links and lift over

dbSNP: rs7019437; hg19: chr9-22134302; COSMIC: COSV60341856;