9-22029548-T-C

Variant names:

• chr9-22029548-T-C
• rs564398
• ENST00000428597.7:n.487T>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.487T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 778,638 control chromosomes in the GnomAD database, including 48,582 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 0.28 (7706 hom., cov: 32)
  • Exomes 𝑓: 0.34 (40876 hom.)
• Consequence: CDKN2B-AS1 ENST00000428597.7 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.156
• Publications: 192 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]

ENSG00000264545 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

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.487T>C		non_coding_transcript_exon	Exon 2 of 19
	CDKN2B-AS1	NR_047532.2		n.487T>C		non_coding_transcript_exon	Exon 2 of 14
	CDKN2B-AS1	NR_047539.2		n.487T>C		non_coding_transcript_exon	Exon 2 of 13

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.487T>C		non_coding_transcript_exon	Exon 2 of 19
	CDKN2B-AS1	ENST00000580576.6	TSL:1	n.487T>C		non_coding_transcript_exon	Exon 2 of 14
	CDKN2B-AS1	ENST00000584351.5	TSL:1	n.487T>C		non_coding_transcript_exon	Exon 2 of 13

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42493 AN: 151930 Hom.: 7700 Cov.: 32

Gnomad AFR AF: 0.0730

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.263

GnomAD2 exomes AF: 0.310 AC: 75443 AN: 243314 AF XY: 0.317

Gnomad AFR exome AF: 0.0628

Gnomad AMR exome AF: 0.162

Gnomad ASJ exome AF: 0.284

Gnomad EAS exome AF: 0.112

Gnomad FIN exome AF: 0.416

Gnomad NFE exome AF: 0.416

Gnomad OTH exome AF: 0.327

GnomAD4 exome AF: 0.343 AC: 214932 AN: 626590 Hom.: 40876 Cov.: 0 AF XY: 0.341 AC XY: 116419 AN XY: 341414

African (AFR) AF: 0.0697 AC: 1231 AN: 17672

American (AMR) AF: 0.169 AC: 7366 AN: 43694

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 5945 AN: 20954

East Asian (EAS) AF: 0.134 AC: 4838 AN: 36040

South Asian (SAS) AF: 0.256 AC: 17840 AN: 69678

European-Finnish (FIN) AF: 0.414 AC: 21497 AN: 51914

Middle Eastern (MID) AF: 0.220 AC: 913 AN: 4146

European-Non Finnish (NFE) AF: 0.413 AC: 144401 AN: 349476

Other (OTH) AF: 0.330 AC: 10901 AN: 33016

GnomAD4 genome AF: 0.280 AC: 42501 AN: 152048 Hom.: 7706 Cov.: 32 AF XY: 0.278 AC XY: 20678 AN XY: 74270

African (AFR) AF: 0.0728 AC: 3022 AN: 41512

American (AMR) AF: 0.212 AC: 3235 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 979 AN: 3472

East Asian (EAS) AF: 0.108 AC: 557 AN: 5172

South Asian (SAS) AF: 0.249 AC: 1199 AN: 4814

European-Finnish (FIN) AF: 0.411 AC: 4335 AN: 10538

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.414 AC: 28154 AN: 67940

Other (OTH) AF: 0.268 AC: 567 AN: 2116

Alfa AF: 0.353 Hom.: 33753

Bravo AF: 0.257

Asia WGS AF: 0.204 AC: 713 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.8
DANN	Benign	0.76
PhyloP100		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs564398; hg19: chr9-22029547;