ENST00000428597.7:n.2448+5912A>G

Variant names:

• chr9-22072265-A-G
• rs10757269
• ENST00000428597.7:n.2448+5912A>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.2448+5912A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.614 in 152,054 control chromosomes in the GnomAD database, including 30,566 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 0.61 (30566 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 48 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 (AFR) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN2B-AS1	NR_003529.4	n.2448+5912A>G		intron_variant	Intron 12 of 18
CDKN2B-AS1	NR_047532.2	n.1075+15878A>G		intron_variant	Intron 6 of 13
CDKN2B-AS1	NR_047533.2	n.645-5414A>G		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000428597.7	n.2448+5912A>G		intron_variant	Intron 12 of 18	1
CDKN2B-AS1	ENST00000455933.8	n.750-5414A>G		intron_variant	Intron 4 of 4	1
CDKN2B-AS1	ENST00000577551.5	n.533+23037A>G		intron_variant	Intron 3 of 6	1

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93343 AN: 151936 Hom.: 30530 Cov.: 32

Gnomad AFR AF: 0.842

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.664

Gnomad EAS AF: 0.792

Gnomad SAS AF: 0.652

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.634

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

GnomAD4 genome AF: 0.614 AC: 93436 AN: 152054 Hom.: 30566 Cov.: 32 AF XY: 0.610 AC XY: 45298 AN XY: 74318

African (AFR) AF: 0.842 AC: 34976 AN: 41516

American (AMR) AF: 0.559 AC: 8536 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.664 AC: 2305 AN: 3470

East Asian (EAS) AF: 0.792 AC: 4094 AN: 5170

South Asian (SAS) AF: 0.651 AC: 3126 AN: 4804

European-Finnish (FIN) AF: 0.444 AC: 4683 AN: 10538

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.496 AC: 33713 AN: 67958

Other (OTH) AF: 0.630 AC: 1332 AN: 2114

Alfa AF: 0.519 Hom.: 24659

Bravo AF: 0.630

Asia WGS AF: 0.707 AC: 2457 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	6.4
DANN	Benign	0.82
PhyloP100		1.1

Splicing

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

Other links and lift over

dbSNP: rs10757269; hg19: chr9-22072264;