ENST00000428597.7:n.2698+5820G>T

Variant names:

• chr9-22103184-G-T
• rs1537372
• ENST00000428597.7:n.2698+5820G>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.2698+5820G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 133,078 control chromosomes in the GnomAD database, including 10,868 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 0.39 (10868 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN2B-AS1	NR_003529.4	n.2698+5820G>T		intron_variant	Intron 14 of 18	ENST00000428597.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000428597.7	n.2698+5820G>T		intron_variant	Intron 14 of 18	1	NR_003529.4

Frequencies

GnomAD3 genomes AF: 0.394 AC: 52339 AN: 132978 Hom.: 10878 Cov.: 25

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.525

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.634

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.393 AC: 52334 AN: 133078 Hom.: 10868 Cov.: 25 AF XY: 0.391 AC XY: 25171 AN XY: 64402

African (AFR) AF: 0.144 AC: 5001 AN: 34792

American (AMR) AF: 0.455 AC: 5988 AN: 13150

Ashkenazi Jewish (ASJ) AF: 0.634 AC: 2021 AN: 3190

East Asian (EAS) AF: 0.525 AC: 2392 AN: 4554

South Asian (SAS) AF: 0.549 AC: 2328 AN: 4244

European-Finnish (FIN) AF: 0.415 AC: 3685 AN: 8872

Middle Eastern (MID) AF: 0.634 AC: 170 AN: 268

European-Non Finnish (NFE) AF: 0.480 AC: 29472 AN: 61384

Other (OTH) AF: 0.480 AC: 874 AN: 1820

Alfa AF: 0.316 Hom.: 1674

Bravo AF: 0.340

Asia WGS AF: 0.449 AC: 1536 AN: 3424

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.24
DANN	Benign	0.62
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;