rs545226

Positions:

• chr9-22012423-G-A
• chr9-22012423-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000399822.2(UBA52P6):​n.269G>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 0.603 in 745,314 control chromosomes in the GnomAD database, including 139,563 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 0.67 (35475 hom., cov: 31)
  • Exomes 𝑓: 0.59 (104088 hom.)
• Consequence: UBA52P6 ENST00000399822.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46

Genes affected

UBA52P6 (HGNC:36763): (ubiquitin A-52 residue ribosomal protein fusion product 1 pseudogene 6)

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDKN2B-AS1	NR_003529.3	n.372-17010G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBA52P6	ENST00000399822.2	n.269G>A		non_coding_transcript_exon_variant	1/1
CDKN2B-AS1	ENST00000650946.1	n.29+17262G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.667 AC: 101288 AN: 151892 Hom.: 35421 Cov.: 31

Gnomad AFR AF: 0.892

Gnomad AMI AF: 0.597

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.610

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.591

Gnomad OTH AF: 0.598

GnomAD4 exome AF: 0.587 AC: 348208 AN: 593306 Hom.: 104088 Cov.: 6 AF XY: 0.582 AC XY: 187968 AN XY: 323150

Gnomad4 AFR exome AF: 0.892

Gnomad4 AMR exome AF: 0.621

Gnomad4 ASJ exome AF: 0.513

Gnomad4 EAS exome AF: 0.418

Gnomad4 SAS exome AF: 0.576

Gnomad4 FIN exome AF: 0.616

Gnomad4 NFE exome AF: 0.588

Gnomad4 OTH exome AF: 0.591

GnomAD4 genome AF: 0.667 AC: 101409 AN: 152008 Hom.: 35475 Cov.: 31 AF XY: 0.665 AC XY: 49367 AN XY: 74278

Gnomad4 AFR AF: 0.892

Gnomad4 AMR AF: 0.607

Gnomad4 ASJ AF: 0.497

Gnomad4 EAS AF: 0.415

Gnomad4 SAS AF: 0.572

Gnomad4 FIN AF: 0.610

Gnomad4 NFE AF: 0.591

Gnomad4 OTH AF: 0.601

Alfa AF: 0.579 Hom.: 29426

Bravo AF: 0.676

Asia WGS AF: 0.551 AC: 1918 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.40
DANN	Benign	0.54

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

Publications

LitVar

Other links and lift over

dbSNP: rs545226; hg19: chr9-22012422; COSMIC: COSV52805102;