chr9-22129580-C-T

Variant names:

• chr9-22129580-C-T
• rs7020996
• ENST00000755351.1:n.302+2178C>T

Variant summary

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

The ENST00000755351.1(CDKN2B-AS1):​n.302+2178C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 151,958 control chromosomes in the GnomAD database, including 3,980 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 0.20 (3980 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000755351.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.377
• Publications: 39 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000755351.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN2B-AS1	ENST00000755351.1		n.302+2178C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30835 AN: 151840 Hom.: 3964 Cov.: 32

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.203 AC: 30897 AN: 151958 Hom.: 3980 Cov.: 32 AF XY: 0.202 AC XY: 15028 AN XY: 74242

African (AFR) AF: 0.349 AC: 14467 AN: 41420

American (AMR) AF: 0.174 AC: 2656 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 466 AN: 3468

East Asian (EAS) AF: 0.389 AC: 2008 AN: 5162

South Asian (SAS) AF: 0.133 AC: 640 AN: 4810

European-Finnish (FIN) AF: 0.115 AC: 1217 AN: 10564

Middle Eastern (MID) AF: 0.171 AC: 50 AN: 292

European-Non Finnish (NFE) AF: 0.131 AC: 8892 AN: 67948

Other (OTH) AF: 0.190 AC: 400 AN: 2108

Alfa AF: 0.157 Hom.: 8365

Bravo AF: 0.216

Asia WGS AF: 0.283 AC: 985 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.8
DANN	Benign	0.51
PhyloP100		0.38

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: rs7020996;

hg19: chr9-22129579;