9-22100177-G-C

Variant names:

• chr9-22100177-G-C
• rs1556516
• ENST00000428597.7:n.2698+2813G>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.2698+2813G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 151,936 control chromosomes in the GnomAD database, including 32,322 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 0.63 (32322 hom., cov: 31)
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• Publications: 56 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN2B-AS1	NR_003529.4	n.2698+2813G>C		intron_variant	Intron 14 of 18	ENST00000428597.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000428597.7	n.2698+2813G>C		intron_variant	Intron 14 of 18	1	NR_003529.4

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95471 AN: 151818 Hom.: 32277 Cov.: 31

Gnomad AFR AF: 0.893

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.660

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.654

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

GnomAD4 genome AF: 0.629 AC: 95574 AN: 151936 Hom.: 32322 Cov.: 31 AF XY: 0.621 AC XY: 46070 AN XY: 74232

African (AFR) AF: 0.893 AC: 37102 AN: 41528

American (AMR) AF: 0.568 AC: 8663 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.660 AC: 2286 AN: 3464

East Asian (EAS) AF: 0.674 AC: 3483 AN: 5170

South Asian (SAS) AF: 0.618 AC: 2978 AN: 4816

European-Finnish (FIN) AF: 0.420 AC: 4416 AN: 10510

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.510 AC: 34603 AN: 67888

Other (OTH) AF: 0.649 AC: 1371 AN: 2112

Alfa AF: 0.370 Hom.: 800

Bravo AF: 0.649

Asia WGS AF: 0.635 AC: 2206 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.33
DANN	Benign	0.27
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs1556516; hg19: chr9-22100176;