ENST00000428597.7:n.2448+14011A>G

Variant names:

• chr9-22080364-A-G
• rs16905613
• ENST00000428597.7:n.2448+14011A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000428597.7(CDKN2B-AS1):​n.2448+14011A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00877 in 152,340 control chromosomes in the GnomAD database, including 18 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 0.0088 (18 hom., cov: 33)
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.140
• Publications: 1 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BS2: High Homozygotes in GnomAd4 at 18 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000428597.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN2B-AS1	NR_003529.4	MANE Select	n.2448+14011A>G		intron	N/A
	CDKN2B-AS1	NR_047532.2		n.1076-11944A>G		intron	N/A
	CDKN2B-AS1	NR_047534.2		n.645-16894A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.2448+14011A>G		intron	N/A
	CDKN2B-AS1	ENST00000577551.5	TSL:1	n.533+31136A>G		intron	N/A
	CDKN2B-AS1	ENST00000580576.6	TSL:1	n.1076-11944A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00878 AC: 1336 AN: 152222 Hom.: 18 Cov.: 33

Gnomad AFR AF: 0.00205

Gnomad AMI AF: 0.0462

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.0231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.0296

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0112

Gnomad OTH AF: 0.00430

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

GnomAD4 genome AF: 0.00877 AC: 1336 AN: 152340 Hom.: 18 Cov.: 33 AF XY: 0.00924 AC XY: 688 AN XY: 74498

African (AFR) AF: 0.00204 AC: 85 AN: 41586

American (AMR) AF: 0.00189 AC: 29 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0231 AC: 80 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00249 AC: 12 AN: 4826

European-Finnish (FIN) AF: 0.0296 AC: 314 AN: 10622

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0112 AC: 763 AN: 68030

Other (OTH) AF: 0.00425 AC: 9 AN: 2116

Alfa AF: 0.0113 Hom.: 11

Bravo AF: 0.00611

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	8.3
DANN	Benign	0.63
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs16905613; hg19: chr9-22080363;