rs10811647

Variant names:

• chr9-22065003-C-G
• rs10811647
• ENST00000428597.7:n.2234-659C>G

Your query was ambiguous. Multiple possible variants found:

• chr9-22065003-C-G
• chr9-22065003-C-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.2234-659C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 151,952 control chromosomes in the GnomAD database, including 11,166 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 0.36 (11166 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.790
• Publications: 23 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=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN2B-AS1	NR_003529.4	n.2234-659C>G		intron_variant	Intron 10 of 18	ENST00000428597.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000428597.7	n.2234-659C>G		intron_variant	Intron 10 of 18	1	NR_003529.4

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55408 AN: 151834 Hom.: 11174 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.568

Gnomad EAS AF: 0.520

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.424

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

GnomAD4 genome AF: 0.365 AC: 55405 AN: 151952 Hom.: 11166 Cov.: 32 AF XY: 0.364 AC XY: 27016 AN XY: 74252

African (AFR) AF: 0.180 AC: 7447 AN: 41456

American (AMR) AF: 0.405 AC: 6182 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.568 AC: 1971 AN: 3472

East Asian (EAS) AF: 0.520 AC: 2681 AN: 5160

South Asian (SAS) AF: 0.443 AC: 2130 AN: 4810

European-Finnish (FIN) AF: 0.423 AC: 4460 AN: 10542

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.428 AC: 29060 AN: 67928

Other (OTH) AF: 0.421 AC: 890 AN: 2114

Alfa AF: 0.376 Hom.: 1407

Bravo AF: 0.354

Asia WGS AF: 0.430 AC: 1496 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	6.9
DANN	Benign	0.67
PhyloP100		-0.79

Splicing

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

Other links and lift over

dbSNP: rs10811647; hg19: chr9-22065002;