chr9-22012423-G-A

Variant names:

• chr9-22012423-G-A
• rs545226
• ENST00000428597.7:n.372-17010G>A

Variant summary

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

The ENST00000428597.7(CDKN2B-AS1):​n.372-17010G>A variant causes a intron 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: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46
• Publications: 19 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]

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

ENSG00000264545 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
UBA52P6		n.22012423G>A		intragenic_variant
CDKN2B-AS1	NR_003529.4	n.372-17010G>A		intron_variant	Intron 1 of 18
CDKN2B-AS1	NR_047532.2	n.372-17010G>A		intron_variant	Intron 1 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000428597.7	n.372-17010G>A		intron_variant	Intron 1 of 18	1
CDKN2B-AS1	ENST00000455933.8	n.340+17262G>A		intron_variant	Intron 1 of 4	1
CDKN2B-AS1	ENST00000577551.5	n.260+17262G>A		intron_variant	Intron 1 of 6	1

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

African (AFR) AF: 0.892 AC: 14940 AN: 16746

American (AMR) AF: 0.621 AC: 24998 AN: 40236

Ashkenazi Jewish (ASJ) AF: 0.513 AC: 9852 AN: 19210

East Asian (EAS) AF: 0.418 AC: 13956 AN: 33416

South Asian (SAS) AF: 0.576 AC: 39081 AN: 67850

European-Finnish (FIN) AF: 0.616 AC: 26412 AN: 42890

Middle Eastern (MID) AF: 0.469 AC: 1166 AN: 2486

European-Non Finnish (NFE) AF: 0.588 AC: 199810 AN: 340036

Other (OTH) AF: 0.591 AC: 17993 AN: 30436

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

African (AFR) AF: 0.892 AC: 37014 AN: 41494

American (AMR) AF: 0.607 AC: 9274 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1725 AN: 3472

East Asian (EAS) AF: 0.415 AC: 2134 AN: 5148

South Asian (SAS) AF: 0.572 AC: 2754 AN: 4814

European-Finnish (FIN) AF: 0.610 AC: 6448 AN: 10574

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.591 AC: 40122 AN: 67930

Other (OTH) AF: 0.601 AC: 1265 AN: 2104

Alfa AF: 0.600 Hom.: 73857

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
PhyloP100		1.5

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