9-22036113-G-T

Variant names:

• chr9-22036113-G-T
• rs1008878
• ENST00000428597.7:n.846+3127G>T

Variant summary

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

The ENST00000428597.7(CDKN2B-AS1):​n.846+3127G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 152,014 control chromosomes in the GnomAD database, including 39,995 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 0.71 (39995 hom., cov: 31)
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.847
• Publications: 24 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 (AFR) allele frequency at 95% confidence interval = 0.902 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.846+3127G>T		intron	N/A
	CDKN2B-AS1	NR_047532.2		n.533+6519G>T		intron	N/A
	CDKN2B-AS1	NR_047533.2		n.372-10638G>T		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.846+3127G>T		intron	N/A
	CDKN2B-AS1	ENST00000455933.8	TSL:1	n.341-10638G>T		intron	N/A
	CDKN2B-AS1	ENST00000577551.5	TSL:1	n.261-10638G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107734 AN: 151896 Hom.: 39933 Cov.: 31

Gnomad AFR AF: 0.909

Gnomad AMI AF: 0.527

Gnomad AMR AF: 0.782

Gnomad ASJ AF: 0.717

Gnomad EAS AF: 0.886

Gnomad SAS AF: 0.754

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.727

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

GnomAD4 genome AF: 0.709 AC: 107849 AN: 152014 Hom.: 39995 Cov.: 31 AF XY: 0.711 AC XY: 52786 AN XY: 74268

African (AFR) AF: 0.910 AC: 37769 AN: 41526

American (AMR) AF: 0.782 AC: 11933 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.717 AC: 2488 AN: 3468

East Asian (EAS) AF: 0.886 AC: 4576 AN: 5164

South Asian (SAS) AF: 0.755 AC: 3636 AN: 4818

European-Finnish (FIN) AF: 0.578 AC: 6095 AN: 10554

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.576 AC: 39104 AN: 67916

Other (OTH) AF: 0.722 AC: 1523 AN: 2110

Alfa AF: 0.625 Hom.: 52117

Bravo AF: 0.731

Asia WGS AF: 0.796 AC: 2765 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.81
DANN	Benign	0.48
PhyloP100		-0.85

Splicing

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

Other links and lift over

dbSNP: rs1008878; hg19: chr9-22036112;