9-22103184-G-A

Variant names:

• chr9-22103184-G-A
• rs1537372
• ENST00000428597.7:n.2698+5820G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000428597.7(CDKN2B-AS1):​n.2698+5820G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 133,212 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00011 (0 hom., cov: 25)
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.865
• Publications: 35 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

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+5820G>A		intron	N/A
	CDKN2B-AS1	NR_047532.2		n.1487+5820G>A		intron	N/A
	CDKN2B-AS1	NR_047534.2		n.751+5820G>A		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+5820G>A		intron	N/A
	CDKN2B-AS1	ENST00000577551.5	TSL:1	n.534-9136G>A		intron	N/A
	CDKN2B-AS1	ENST00000580576.6	TSL:1	n.1487+5820G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000113 AC: 15 AN: 133112 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.000317

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000152

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000325

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.000113 AC: 15 AN: 133212 Hom.: 0 Cov.: 25 AF XY: 0.000124 AC XY: 8 AN XY: 64474

African (AFR) AF: 0.000316 AC: 11 AN: 34822

American (AMR) AF: 0.000152 AC: 2 AN: 13166

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3190

East Asian (EAS) AF: 0.00 AC: 0 AN: 4560

South Asian (SAS) AF: 0.00 AC: 0 AN: 4246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8894

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 268

European-Non Finnish (NFE) AF: 0.0000326 AC: 2 AN: 61440

Other (OTH) AF: 0.00 AC: 0 AN: 1822

Alfa AF: 0.00 Hom.: 1674

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.89
DANN	Benign	0.57
PhyloP100		-0.86

Splicing

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

Other links and lift over

dbSNP: rs1537372; hg19: chr9-22103183;