ENST00000428597.7:n.2448+2300G>A

Variant names:

• chr9-22068653-G-A
• rs4977756
• ENST00000428597.7:n.2448+2300G>A

Variant summary

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

The ENST00000428597.7(CDKN2B-AS1):​n.2448+2300G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 152,142 control chromosomes in the GnomAD database, including 32,248 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 0.65 (32248 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0130
• Publications: 183 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN2B-AS1	NR_003529.4	n.2448+2300G>A		intron_variant	Intron 12 of 18
CDKN2B-AS1	NR_047532.2	n.1075+12266G>A		intron_variant	Intron 6 of 13
CDKN2B-AS1	NR_047533.2	n.645-9026G>A		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000428597.7	n.2448+2300G>A		intron_variant	Intron 12 of 18	1
CDKN2B-AS1	ENST00000455933.8	n.750-9026G>A		intron_variant	Intron 4 of 4	1
CDKN2B-AS1	ENST00000577551.5	n.533+19425G>A		intron_variant	Intron 3 of 6	1

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98556 AN: 152022 Hom.: 32230 Cov.: 32

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.758

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.779

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.674

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

GnomAD4 genome AF: 0.648 AC: 98606 AN: 152142 Hom.: 32248 Cov.: 32 AF XY: 0.650 AC XY: 48366 AN XY: 74364

African (AFR) AF: 0.651 AC: 27010 AN: 41514

American (AMR) AF: 0.758 AC: 11589 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.752 AC: 2610 AN: 3470

East Asian (EAS) AF: 0.779 AC: 4030 AN: 5170

South Asian (SAS) AF: 0.759 AC: 3663 AN: 4826

European-Finnish (FIN) AF: 0.617 AC: 6537 AN: 10598

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.603 AC: 41018 AN: 67972

Other (OTH) AF: 0.670 AC: 1410 AN: 2106

Alfa AF: 0.620 Hom.: 131334

Bravo AF: 0.657

Asia WGS AF: 0.725 AC: 2517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.64
PhyloP100		0.013

Splicing

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

Other links and lift over

dbSNP: rs4977756; hg19: chr9-22068652;