rs10757272

Variant names:

• chr9-22088261-C-T
• rs10757272
• ENST00000428597.7:n.2449-8111C>T

Variant summary

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

The ENST00000428597.7(CDKN2B-AS1):​n.2449-8111C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 151,912 control chromosomes in the GnomAD database, including 14,779 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 0.42 (14779 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82
• Publications: 80 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN2B-AS1	NR_003529.4	n.2449-8111C>T		intron_variant	Intron 12 of 18
CDKN2B-AS1	NR_047532.2	n.1076-4047C>T		intron_variant	Intron 6 of 13
CDKN2B-AS1	NR_047534.2	n.645-8997C>T		intron_variant	Intron 3 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000428597.7	n.2449-8111C>T		intron_variant	Intron 12 of 18	1
CDKN2B-AS1	ENST00000577551.5	n.534-24059C>T		intron_variant	Intron 3 of 6	1
CDKN2B-AS1	ENST00000580576.6	n.1076-4047C>T		intron_variant	Intron 6 of 13	1

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63978 AN: 151794 Hom.: 14793 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.666

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.481

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

GnomAD4 genome AF: 0.421 AC: 63985 AN: 151912 Hom.: 14779 Cov.: 32 AF XY: 0.419 AC XY: 31094 AN XY: 74266

African (AFR) AF: 0.219 AC: 9082 AN: 41398

American (AMR) AF: 0.459 AC: 7008 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.620 AC: 2153 AN: 3470

East Asian (EAS) AF: 0.666 AC: 3440 AN: 5166

South Asian (SAS) AF: 0.585 AC: 2819 AN: 4816

European-Finnish (FIN) AF: 0.407 AC: 4287 AN: 10546

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.494 AC: 33552 AN: 67934

Other (OTH) AF: 0.478 AC: 1009 AN: 2110

Alfa AF: 0.470 Hom.: 53146

Bravo AF: 0.413

Asia WGS AF: 0.566 AC: 1967 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.58
DANN	Benign	0.87
PhyloP100		-1.8

Splicing

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

Other links and lift over

dbSNP: rs10757272; hg19: chr9-22088260;