rs13298881

Variant names:

• chr9-22012052-T-C
• rs13298881
• ENST00000428597.7:n.371+16891T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000428597.7(CDKN2B-AS1):​n.371+16891T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0808 in 582,954 control chromosomes in the GnomAD database, including 2,323 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 0.076 (588 hom., cov: 32)
  • Exomes 𝑓: 0.082 (1735 hom.)
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.60
• Publications: 17 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]

ENSG00000264545 (HGNC:):

UBA52P6 (HGNC:36763): (ubiquitin A-52 residue ribosomal protein fusion product 1 pseudogene 6)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000428597.7. 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_003529.4	MANE Select	n.371+16891T>C		intron	N/A
	CDKN2B-AS1	NR_047532.2		n.371+16891T>C		intron	N/A
	CDKN2B-AS1	NR_047533.2		n.371+16891T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.371+16891T>C		intron	N/A
	CDKN2B-AS1	ENST00000455933.8	TSL:1	n.340+16891T>C		intron	N/A
	CDKN2B-AS1	ENST00000577551.5	TSL:1	n.260+16891T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0763 AC: 11612 AN: 152134 Hom.: 589 Cov.: 32

Gnomad AFR AF: 0.0387

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.0880

Gnomad ASJ AF: 0.0813

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0240

Gnomad FIN AF: 0.0643

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.0919

GnomAD4 exome AF: 0.0825 AC: 35517 AN: 430702 Hom.: 1735 AF XY: 0.0800 AC XY: 18175 AN XY: 227286

African (AFR) AF: 0.0375 AC: 434 AN: 11572

American (AMR) AF: 0.0768 AC: 1336 AN: 17390

Ashkenazi Jewish (ASJ) AF: 0.0819 AC: 1021 AN: 12468

East Asian (EAS) AF: 0.0000698 AC: 2 AN: 28646

South Asian (SAS) AF: 0.0268 AC: 1180 AN: 43980

European-Finnish (FIN) AF: 0.0699 AC: 2625 AN: 37532

Middle Eastern (MID) AF: 0.111 AC: 197 AN: 1768

European-Non Finnish (NFE) AF: 0.105 AC: 26645 AN: 253708

Other (OTH) AF: 0.0879 AC: 2077 AN: 23638

GnomAD4 genome AF: 0.0763 AC: 11611 AN: 152252 Hom.: 588 Cov.: 32 AF XY: 0.0715 AC XY: 5327 AN XY: 74460

African (AFR) AF: 0.0386 AC: 1603 AN: 41560

American (AMR) AF: 0.0879 AC: 1344 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0813 AC: 282 AN: 3470

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5186

South Asian (SAS) AF: 0.0236 AC: 114 AN: 4828

European-Finnish (FIN) AF: 0.0643 AC: 682 AN: 10606

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7184 AN: 68006

Other (OTH) AF: 0.0914 AC: 193 AN: 2112

Alfa AF: 0.102 Hom.: 1592

Bravo AF: 0.0792

Asia WGS AF: 0.0140 AC: 49 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	11
DANN	Benign	0.94
PhyloP100		1.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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: rs13298881;

hg19: chr9-22012051;