9-22134173-C-T

Variant names:

• chr9-22134173-C-T
• rs10757283
• ENST00000755351.1:n.302+6771C>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+6771C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 151,976 control chromosomes in the GnomAD database, including 15,582 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 0.45 (15582 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000755351.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.58
• Publications: 34 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.604 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+6771C>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68532 AN: 151858 Hom.: 15561 Cov.: 32

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.473

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

GnomAD4 genome AF: 0.451 AC: 68593 AN: 151976 Hom.: 15582 Cov.: 32 AF XY: 0.453 AC XY: 33625 AN XY: 74272

African (AFR) AF: 0.468 AC: 19401 AN: 41432

American (AMR) AF: 0.431 AC: 6584 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 1594 AN: 3470

East Asian (EAS) AF: 0.622 AC: 3210 AN: 5164

South Asian (SAS) AF: 0.441 AC: 2130 AN: 4826

European-Finnish (FIN) AF: 0.471 AC: 4962 AN: 10528

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.429 AC: 29151 AN: 67970

Other (OTH) AF: 0.472 AC: 995 AN: 2106

Alfa AF: 0.444 Hom.: 35126

Bravo AF: 0.452

Asia WGS AF: 0.550 AC: 1914 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.082
DANN	Benign	0.53
PhyloP100		-2.6

Splicing

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

Other links and lift over

dbSNP: rs10757283; hg19: chr9-22134172; COSMIC: COSV60341848;