ENST00000650946.1:n.439-2630C>T

Variant names:

• chr9-22124473-C-T
• rs10811656
• ENST00000650946.1:n.439-2630C>T

Variant summary

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

The ENST00000650946.1(CDKN2B-AS1):​n.439-2630C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 151,750 control chromosomes in the GnomAD database, including 16,783 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 0.47 (16783 hom., cov: 33)
• Consequence: CDKN2B-AS1 ENST00000650946.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0110
• Publications: 50 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=-0.71).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000650946.1. 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_185859.1		n.781-2630C>T		intron	N/A
	CDKN2B-AS1	NR_185867.1		n.1256-2630C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN2B-AS1	ENST00000650946.1		n.439-2630C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71189 AN: 151632 Hom.: 16771 Cov.: 33

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.483

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.524

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

GnomAD4 genome AF: 0.469 AC: 71233 AN: 151750 Hom.: 16783 Cov.: 33 AF XY: 0.462 AC XY: 34286 AN XY: 74154

African (AFR) AF: 0.433 AC: 17934 AN: 41418

American (AMR) AF: 0.513 AC: 7830 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 2063 AN: 3460

East Asian (EAS) AF: 0.400 AC: 2062 AN: 5160

South Asian (SAS) AF: 0.500 AC: 2405 AN: 4810

European-Finnish (FIN) AF: 0.405 AC: 4251 AN: 10498

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.486 AC: 32989 AN: 67836

Other (OTH) AF: 0.521 AC: 1094 AN: 2098

Alfa AF: 0.464 Hom.: 13220

Bravo AF: 0.475

Asia WGS AF: 0.456 AC: 1586 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	9.2
DANN	Benign	0.82
PhyloP100		-0.011

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10811656;

hg19: chr9-22124472;

COSMIC: COSV69592461;