9-22082381-A-G

Variant names:

• chr9-22082381-A-G
• rs10965228
• ENST00000428597.7:n.2449-13991A>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.2449-13991A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0649 in 152,310 control chromosomes in the GnomAD database, including 453 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 0.065 (453 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.641
• Publications: 12 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN2B-AS1	NR_003529.4	n.2449-13991A>G		intron_variant	Intron 12 of 18
CDKN2B-AS1	NR_047532.2	n.1076-9927A>G		intron_variant	Intron 6 of 13
CDKN2B-AS1	NR_047534.2	n.645-14877A>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.2449-13991A>G		intron_variant	Intron 12 of 18	1
CDKN2B-AS1	ENST00000577551.5	n.534-29939A>G		intron_variant	Intron 3 of 6	1
CDKN2B-AS1	ENST00000580576.6	n.1076-9927A>G		intron_variant	Intron 6 of 13	1

Frequencies

GnomAD3 genomes AF: 0.0650 AC: 9888 AN: 152192 Hom.: 453 Cov.: 32

Gnomad AFR AF: 0.0177

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.0580

Gnomad ASJ AF: 0.0706

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0485

Gnomad FIN AF: 0.0708

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0987

Gnomad OTH AF: 0.0755

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

GnomAD4 genome AF: 0.0649 AC: 9889 AN: 152310 Hom.: 453 Cov.: 32 AF XY: 0.0643 AC XY: 4791 AN XY: 74474

African (AFR) AF: 0.0177 AC: 735 AN: 41584

American (AMR) AF: 0.0579 AC: 886 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0706 AC: 245 AN: 3472

East Asian (EAS) AF: 0.000964 AC: 5 AN: 5186

South Asian (SAS) AF: 0.0493 AC: 238 AN: 4824

European-Finnish (FIN) AF: 0.0708 AC: 751 AN: 10612

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0987 AC: 6713 AN: 68016

Other (OTH) AF: 0.0747 AC: 158 AN: 2116

Alfa AF: 0.0825 Hom.: 331

Bravo AF: 0.0619

Asia WGS AF: 0.0190 AC: 67 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.81
DANN	Benign	0.55
PhyloP100		-0.64

Splicing

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

Other links and lift over

dbSNP: rs10965228; hg19: chr9-22082380;