ENST00000755351.1:n.303-40963T>C

Variant names:

• chr9-22169701-T-C
• rs1537377
• ENST00000755351.1:n.303-40963T>C

Variant summary

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

The ENST00000755351.1(CDKN2B-AS1):​n.303-40963T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 152,066 control chromosomes in the GnomAD database, including 15,570 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 0.44 (15570 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000755351.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.247
• Publications: 45 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.573 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.303-40963T>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.441 AC: 67044 AN: 151948 Hom.: 15549 Cov.: 32

Gnomad AFR AF: 0.580

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.393

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

GnomAD4 genome AF: 0.441 AC: 67114 AN: 152066 Hom.: 15570 Cov.: 32 AF XY: 0.442 AC XY: 32882 AN XY: 74336

African (AFR) AF: 0.579 AC: 24044 AN: 41492

American (AMR) AF: 0.397 AC: 6058 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 960 AN: 3466

East Asian (EAS) AF: 0.309 AC: 1603 AN: 5180

South Asian (SAS) AF: 0.583 AC: 2811 AN: 4822

European-Finnish (FIN) AF: 0.382 AC: 4032 AN: 10556

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.391 AC: 26571 AN: 67960

Other (OTH) AF: 0.394 AC: 834 AN: 2116

Alfa AF: 0.414 Hom.: 32590

Bravo AF: 0.443

Asia WGS AF: 0.507 AC: 1763 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.5
DANN	Benign	0.77
PhyloP100		0.25

Splicing

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

Other links and lift over

dbSNP: rs1537377; hg19: chr9-22169700; COSMIC: COSV60341937;