9-22096056-A-G

Variant names:

• chr9-22096056-A-G
• rs10757274
• ENST00000428597.7:n.2449-316A>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.2449-316A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 151,878 control chromosomes in the GnomAD database, including 14,245 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 0.41 (14245 hom., cov: 30)
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: 1.29
• Publications: 272 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=-0.89).
• 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.2449-316A>G		intron	N/A
	CDKN2B-AS1	NR_047532.2		n.1238-316A>G		intron	N/A
	CDKN2B-AS1	NR_047534.2		n.645-1202A>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.2449-316A>G		intron	N/A
	CDKN2B-AS1	ENST00000577551.5	TSL:1	n.534-16264A>G		intron	N/A
	CDKN2B-AS1	ENST00000580576.6	TSL:1	n.1238-316A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.415 AC: 63020 AN: 151760 Hom.: 14255 Cov.: 30

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.623

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.524

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.482

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

GnomAD4 genome AF: 0.415 AC: 63029 AN: 151878 Hom.: 14245 Cov.: 30 AF XY: 0.412 AC XY: 30571 AN XY: 74230

African (AFR) AF: 0.217 AC: 9001 AN: 41432

American (AMR) AF: 0.457 AC: 6969 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.623 AC: 2156 AN: 3462

East Asian (EAS) AF: 0.484 AC: 2488 AN: 5142

South Asian (SAS) AF: 0.523 AC: 2517 AN: 4814

European-Finnish (FIN) AF: 0.434 AC: 4566 AN: 10528

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.496 AC: 33691 AN: 67952

Other (OTH) AF: 0.478 AC: 1005 AN: 2102

Alfa AF: 0.469 Hom.: 71864

Bravo AF: 0.406

Asia WGS AF: 0.493 AC: 1714 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	-0.89
CADD	Benign	11
DANN	Benign	0.76
PhyloP100		1.3

Splicing

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

Other links and lift over

dbSNP: rs10757274; hg19: chr9-22096055;