rs10757279

Variant names:

• chr9-22124631-A-G
• rs10757279
• ENST00000650946.1:n.439-2472A>G

Your query was ambiguous. Multiple possible variants found:

• chr9-22124631-A-G
• chr9-22124631-A-T

Variant summary

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

The ENST00000650946.1(CDKN2B-AS1):​n.439-2472A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 152,060 control chromosomes in the GnomAD database, including 13,850 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 0.41 (13850 hom., cov: 33)
• Consequence: CDKN2B-AS1 ENST00000650946.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.337
• Publications: 25 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN2B-AS1	NR_185859.1	n.781-2472A>G		intron_variant	Intron 4 of 4
CDKN2B-AS1	NR_185867.1	n.1256-2472A>G		intron_variant	Intron 6 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000650946.1	n.439-2472A>G		intron_variant	Intron 4 of 4

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61754 AN: 151942 Hom.: 13856 Cov.: 33

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.494

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.472

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

GnomAD4 genome AF: 0.406 AC: 61761 AN: 152060 Hom.: 13850 Cov.: 33 AF XY: 0.404 AC XY: 30005 AN XY: 74348

African (AFR) AF: 0.196 AC: 8127 AN: 41488

American (AMR) AF: 0.480 AC: 7332 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 2036 AN: 3472

East Asian (EAS) AF: 0.508 AC: 2629 AN: 5178

South Asian (SAS) AF: 0.526 AC: 2535 AN: 4818

European-Finnish (FIN) AF: 0.417 AC: 4395 AN: 10552

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.487 AC: 33108 AN: 67962

Other (OTH) AF: 0.468 AC: 988 AN: 2112

Alfa AF: 0.420 Hom.: 7819

Bravo AF: 0.399

Asia WGS AF: 0.495 AC: 1723 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.4
DANN	Benign	0.70
PhyloP100		0.34

Splicing

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

Other links and lift over

dbSNP: rs10757279; hg19: chr9-22124630; COSMIC: COSV69592467;