ENST00000428597.7:n.533+845A>G

Variant names:

• chr9-22030439-A-G
• rs662463
• ENST00000428597.7:n.533+845A>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.533+845A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.899 in 152,162 control chromosomes in the GnomAD database, including 61,442 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 0.90 (61441 hom., cov: 31)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0880
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.958 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.533+845A>G		intron	N/A
	CDKN2B-AS1	NR_047532.2		n.533+845A>G		intron	N/A
	CDKN2B-AS1	NR_047533.2		n.372-16312A>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.533+845A>G		intron	N/A
	CDKN2B-AS1	ENST00000455933.8	TSL:1	n.341-16312A>G		intron	N/A
	CDKN2B-AS1	ENST00000577551.5	TSL:1	n.261-16312A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.899 AC: 136623 AN: 152042 Hom.: 61402 Cov.: 31

Gnomad AFR AF: 0.869

Gnomad AMI AF: 0.955

Gnomad AMR AF: 0.917

Gnomad ASJ AF: 0.904

Gnomad EAS AF: 0.981

Gnomad SAS AF: 0.952

Gnomad FIN AF: 0.916

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.899

Gnomad OTH AF: 0.903

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.899 AC: 136719 AN: 152160 Hom.: 61441 Cov.: 31 AF XY: 0.901 AC XY: 67013 AN XY: 74398

African (AFR) AF: 0.869 AC: 36041 AN: 41490

American (AMR) AF: 0.918 AC: 14030 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.904 AC: 3137 AN: 3470

East Asian (EAS) AF: 0.980 AC: 5073 AN: 5174

South Asian (SAS) AF: 0.952 AC: 4592 AN: 4824

European-Finnish (FIN) AF: 0.916 AC: 9706 AN: 10596

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.899 AC: 61107 AN: 68000

Other (OTH) AF: 0.904 AC: 1909 AN: 2112

Alfa AF: 0.900 Hom.: 44473

Bravo AF: 0.898

Asia WGS AF: 0.954 AC: 3315 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.0
DANN	Benign	0.88
PhyloP100		-0.088

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs662463; hg19: chr9-22030438;