ENST00000428597.7:n.534-521T>G

Variant names:

• chr9-22032153-T-G
• rs634537
• ENST00000428597.7:n.534-521T>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.534-521T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 151,896 control chromosomes in the GnomAD database, including 7,658 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 0.28 (7658 hom., cov: 30)
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.49
• Publications: 38 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 (NFE) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN2B-AS1	NR_003529.4	n.534-521T>G		intron_variant	Intron 2 of 18
CDKN2B-AS1	NR_047532.2	n.533+2559T>G		intron_variant	Intron 2 of 13
CDKN2B-AS1	NR_047533.2	n.372-14598T>G		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000428597.7	n.534-521T>G		intron_variant	Intron 2 of 18	1
CDKN2B-AS1	ENST00000455933.8	n.341-14598T>G		intron_variant	Intron 1 of 4	1
CDKN2B-AS1	ENST00000577551.5	n.261-14598T>G		intron_variant	Intron 1 of 6	1

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42346 AN: 151778 Hom.: 7652 Cov.: 30

Gnomad AFR AF: 0.0731

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.279 AC: 42355 AN: 151896 Hom.: 7658 Cov.: 30 AF XY: 0.278 AC XY: 20599 AN XY: 74200

African (AFR) AF: 0.0729 AC: 3026 AN: 41502

American (AMR) AF: 0.212 AC: 3230 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 973 AN: 3460

East Asian (EAS) AF: 0.108 AC: 558 AN: 5160

South Asian (SAS) AF: 0.247 AC: 1188 AN: 4802

European-Finnish (FIN) AF: 0.409 AC: 4291 AN: 10496

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.413 AC: 28072 AN: 67902

Other (OTH) AF: 0.268 AC: 566 AN: 2110

Alfa AF: 0.333 Hom.: 8120

Bravo AF: 0.257

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.055
DANN	Benign	0.65
PhyloP100		-2.5

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: rs634537; hg19: chr9-22032152;