ENST00000428597.7:n.2449-14521C>T

Variant names:

• chr9-22081851-C-T
• rs6475606
• ENST00000428597.7:n.2449-14521C>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.2449-14521C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 152,128 control chromosomes in the GnomAD database, including 31,472 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 0.62 (31472 hom., cov: 33)
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.208
• Publications: 75 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.882 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN2B-AS1	NR_003529.4	MANE Select	n.2449-14521C>T		intron	N/A
	CDKN2B-AS1	NR_047532.2		n.1076-10457C>T		intron	N/A
	CDKN2B-AS1	NR_047534.2		n.645-15407C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.2449-14521C>T		intron	N/A
	CDKN2B-AS1	ENST00000577551.5	TSL:1	n.534-30469C>T		intron	N/A
	CDKN2B-AS1	ENST00000580576.6	TSL:1	n.1076-10457C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.618 AC: 93870 AN: 152010 Hom.: 31430 Cov.: 33

Gnomad AFR AF: 0.890

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.696

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.638

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

GnomAD4 genome AF: 0.618 AC: 93969 AN: 152128 Hom.: 31472 Cov.: 33 AF XY: 0.609 AC XY: 45291 AN XY: 74352

African (AFR) AF: 0.890 AC: 36966 AN: 41538

American (AMR) AF: 0.553 AC: 8449 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 2238 AN: 3470

East Asian (EAS) AF: 0.696 AC: 3599 AN: 5174

South Asian (SAS) AF: 0.612 AC: 2948 AN: 4818

European-Finnish (FIN) AF: 0.413 AC: 4372 AN: 10580

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.492 AC: 33435 AN: 67944

Other (OTH) AF: 0.634 AC: 1341 AN: 2116

Alfa AF: 0.541 Hom.: 53046

Bravo AF: 0.637

Asia WGS AF: 0.648 AC: 2254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.61
PhyloP100		0.21

Splicing

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

Other links and lift over

dbSNP: rs6475606; hg19: chr9-22081850; COSMIC: COSV70107257;