ENST00000428597.7:n.2774+205T>C

Variant names:

• chr9-22112600-T-C
• rs10511701
• ENST00000428597.7:n.2774+205T>C

Variant summary

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

The ENST00000428597.7(CDKN2B-AS1):​n.2774+205T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 152,040 control chromosomes in the GnomAD database, including 26,943 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 0.59 (26943 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0490
• Publications: 26 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN2B-AS1	NR_003529.4	n.2774+205T>C		intron_variant	Intron 15 of 18
CDKN2B-AS1	NR_047532.2	n.1563+205T>C		intron_variant	Intron 10 of 13
CDKN2B-AS1	NR_047534.2	n.827+205T>C		intron_variant	Intron 5 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000428597.7	n.2774+205T>C		intron_variant	Intron 15 of 18	1
CDKN2B-AS1	ENST00000577551.5	n.609+205T>C		intron_variant	Intron 4 of 6	1
CDKN2B-AS1	ENST00000580576.6	n.1563+205T>C		intron_variant	Intron 10 of 13	1

Frequencies

GnomAD3 genomes AF: 0.587 AC: 89195 AN: 151922 Hom.: 26920 Cov.: 32

Gnomad AFR AF: 0.730

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.670

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.610

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

GnomAD4 genome AF: 0.587 AC: 89275 AN: 152040 Hom.: 26943 Cov.: 32 AF XY: 0.580 AC XY: 43081 AN XY: 74312

African (AFR) AF: 0.731 AC: 30311 AN: 41488

American (AMR) AF: 0.578 AC: 8833 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.652 AC: 2261 AN: 3468

East Asian (EAS) AF: 0.670 AC: 3459 AN: 5164

South Asian (SAS) AF: 0.600 AC: 2886 AN: 4810

European-Finnish (FIN) AF: 0.427 AC: 4507 AN: 10556

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.516 AC: 35081 AN: 67954

Other (OTH) AF: 0.607 AC: 1281 AN: 2112

Alfa AF: 0.560 Hom.: 17331

Bravo AF: 0.603

Asia WGS AF: 0.616 AC: 2142 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.8
DANN	Benign	0.77
PhyloP100		0.049

Splicing

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

Other links and lift over

dbSNP: rs10511701; hg19: chr9-22112599;