rs10965215

chr9-22029446-G-Achr9-22029446-G-Cchr9-22029446-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NR_003529.3(CDKN2B-AS1):n.385G>A 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 0.516 in 778,978 control chromosomes in the GnomAD database, including 107,992 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.47 (17825 hom., cov: 31)
  • Exomes 𝑓: 0.53 (90167 hom.)
• Consequence: CDKN2B-AS1 NR_003529.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0590

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 9-22029446-G-A is Benign according to our data. Variant chr9-22029446-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDKN2B-AS1	NR_003529.3	n.385G>A		non_coding_transcript_exon_variant	2/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDKN2B-AS1	ENST00000650946.1	n.30-17305G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71448 AN: 151836 Hom.: 17828 Cov.: 31

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.605

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.519

GnomAD3 exomes AF: 0.547 AC: 133278 AN: 243722 Hom.: 38391 AF XY: 0.546 AC XY: 72902 AN XY: 133590

Gnomad AFR exome AF: 0.324

Gnomad AMR exome AF: 0.754

Gnomad ASJ exome AF: 0.602

Gnomad EAS exome AF: 0.669

Gnomad SAS exome AF: 0.625

Gnomad FIN exome AF: 0.497

Gnomad NFE exome AF: 0.474

Gnomad OTH exome AF: 0.545

GnomAD4 exome AF: 0.527 AC: 330256 AN: 627024 Hom.: 90167 Cov.: 0 AF XY: 0.532 AC XY: 181626 AN XY: 341636

Gnomad4 AFR exome AF: 0.330

Gnomad4 AMR exome AF: 0.740

Gnomad4 ASJ exome AF: 0.603

Gnomad4 EAS exome AF: 0.656

Gnomad4 SAS exome AF: 0.624

Gnomad4 FIN exome AF: 0.501

Gnomad4 NFE exome AF: 0.476

Gnomad4 OTH exome AF: 0.521

GnomAD4 genome AF: 0.470 AC: 71461 AN: 151954 Hom.: 17825 Cov.: 31 AF XY: 0.477 AC XY: 35431 AN XY: 74270

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.644

Gnomad4 ASJ AF: 0.605

Gnomad4 EAS AF: 0.675

Gnomad4 SAS AF: 0.635

Gnomad4 FIN AF: 0.502

Gnomad4 NFE AF: 0.475

Gnomad4 OTH AF: 0.515

Alfa AF: 0.479 Hom.: 17344

Bravo AF: 0.474

Asia WGS AF: 0.622 AC: 2161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	7.5
Dann	Benign	0.92

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs10965215; hg19: chr9-22029445;