9-22098575-A-G

Variant names:

• chr9-22098575-A-G
• rs4977574
• ENST00000428597.7:n.2698+1211A>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.2698+1211A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 152,068 control chromosomes in the GnomAD database, including 13,949 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency: Genomes: 𝑓 0.40 (13949 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: -0.0800
• Publications: 308 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=-0.74).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.506 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.2698+1211A>G		intron	N/A
	CDKN2B-AS1	NR_047532.2		n.1487+1211A>G		intron	N/A
	CDKN2B-AS1	NR_047534.2		n.751+1211A>G		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.2698+1211A>G		intron	N/A
	CDKN2B-AS1	ENST00000577551.5	TSL:1	n.534-13745A>G		intron	N/A
	CDKN2B-AS1	ENST00000580576.6	TSL:1	n.1487+1211A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61532 AN: 151950 Hom.: 13962 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.495

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.623

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.475

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

GnomAD4 genome AF: 0.405 AC: 61534 AN: 152068 Hom.: 13949 Cov.: 32 AF XY: 0.402 AC XY: 29893 AN XY: 74348

African (AFR) AF: 0.182 AC: 7563 AN: 41510

American (AMR) AF: 0.451 AC: 6886 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.623 AC: 2159 AN: 3464

East Asian (EAS) AF: 0.485 AC: 2505 AN: 5168

South Asian (SAS) AF: 0.523 AC: 2517 AN: 4810

European-Finnish (FIN) AF: 0.433 AC: 4585 AN: 10578

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.496 AC: 33689 AN: 67960

Other (OTH) AF: 0.471 AC: 993 AN: 2108

Alfa AF: 0.470 Hom.: 80431

Bravo AF: 0.394

Asia WGS AF: 0.490 AC: 1705 AN: 3478

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Three Vessel Coronary Disease Other:1

Department of Cardiology, Chinese Academy of Medical Sciences, Fuwai Hospital

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.3
DANN	Benign	0.92
PhyloP100		-0.080

Splicing

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

Other links and lift over

dbSNP: rs4977574; hg19: chr9-22098574;