rs10965227

Variant names:

• chr9-22081797-A-G
• rs10965227
• ENST00000428597.7:n.2449-14575A>G

Variant summary

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

The ENST00000428597.7(CDKN2B-AS1):​n.2449-14575A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,286 control chromosomes in the GnomAD database, including 3,127 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 0.17 (3127 hom., cov: 33)
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55
• Publications: 10 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN2B-AS1	NR_003529.4	n.2449-14575A>G		intron_variant	Intron 12 of 18
CDKN2B-AS1	NR_047532.2	n.1076-10511A>G		intron_variant	Intron 6 of 13
CDKN2B-AS1	NR_047534.2	n.645-15461A>G		intron_variant	Intron 3 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000428597.7	n.2449-14575A>G		intron_variant	Intron 12 of 18	1
CDKN2B-AS1	ENST00000577551.5	n.534-30523A>G		intron_variant	Intron 3 of 6	1
CDKN2B-AS1	ENST00000580576.6	n.1076-10511A>G		intron_variant	Intron 6 of 13	1

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26573 AN: 152168 Hom.: 3124 Cov.: 33

Gnomad AFR AF: 0.0418

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.184

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

GnomAD4 genome AF: 0.175 AC: 26585 AN: 152286 Hom.: 3127 Cov.: 33 AF XY: 0.181 AC XY: 13445 AN XY: 74466

African (AFR) AF: 0.0417 AC: 1732 AN: 41582

American (AMR) AF: 0.360 AC: 5505 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 559 AN: 3468

East Asian (EAS) AF: 0.146 AC: 756 AN: 5182

South Asian (SAS) AF: 0.180 AC: 871 AN: 4832

European-Finnish (FIN) AF: 0.225 AC: 2388 AN: 10600

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

European-Non Finnish (NFE) AF: 0.206 AC: 14023 AN: 68010

Other (OTH) AF: 0.183 AC: 386 AN: 2114

Alfa AF: 0.198 Hom.: 3074

Bravo AF: 0.184

Asia WGS AF: 0.155 AC: 539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	10
DANN	Benign	0.60
PhyloP100		1.5

Splicing

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

Other links and lift over

dbSNP: rs10965227; hg19: chr9-22081796;