ENST00000755351.1:n.302+17129T>G

Variant names:

• chr9-22144531-T-G
• rs7853656
• ENST00000755351.1:n.302+17129T>G

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+17129T>G 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 151,878 control chromosomes in the GnomAD database, including 3,517 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 (3517 hom., cov: 31)
• Consequence: CDKN2B-AS1 ENST00000755351.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.327
• Publications: 2 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000755351.1	n.302+17129T>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30718 AN: 151760 Hom.: 3509 Cov.: 31

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.0792

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.203 AC: 30769 AN: 151878 Hom.: 3517 Cov.: 31 AF XY: 0.199 AC XY: 14813 AN XY: 74270

African (AFR) AF: 0.279 AC: 11546 AN: 41426

American (AMR) AF: 0.154 AC: 2355 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 633 AN: 3462

East Asian (EAS) AF: 0.0792 AC: 411 AN: 5188

South Asian (SAS) AF: 0.266 AC: 1278 AN: 4808

European-Finnish (FIN) AF: 0.119 AC: 1259 AN: 10588

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12646 AN: 67842

Other (OTH) AF: 0.211 AC: 445 AN: 2112

Alfa AF: 0.193 Hom.: 2591

Bravo AF: 0.205

Asia WGS AF: 0.186 AC: 650 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.9
DANN	Benign	0.50
PhyloP100		-0.33

Splicing

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

Other links and lift over

dbSNP: rs7853656; hg19: chr9-22144530; COSMIC: COSV69451115;