rs16905599

Variant names:

• chr9-22069145-G-A
• rs16905599
• ENST00000428597.7:n.2448+2792G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-22069145-G-A
• chr9-22069145-G-T

Variant summary

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

The ENST00000428597.7(CDKN2B-AS1):​n.2448+2792G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,074 control chromosomes in the GnomAD database, including 2,017 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 0.14 (2017 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.955
• Publications: 25 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.249 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.2448+2792G>A		intron	N/A
	CDKN2B-AS1	NR_047532.2		n.1075+12758G>A		intron	N/A
	CDKN2B-AS1	NR_047533.2		n.645-8534G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.2448+2792G>A		intron	N/A
	CDKN2B-AS1	ENST00000455933.8	TSL:1	n.750-8534G>A		intron	N/A
	CDKN2B-AS1	ENST00000577551.5	TSL:1	n.533+19917G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21789 AN: 151956 Hom.: 2019 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.0527

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.0876

Gnomad EAS AF: 0.0884

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0789

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.143 AC: 21806 AN: 152074 Hom.: 2017 Cov.: 32 AF XY: 0.148 AC XY: 10969 AN XY: 74342

African (AFR) AF: 0.225 AC: 9312 AN: 41464

American (AMR) AF: 0.256 AC: 3904 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0876 AC: 304 AN: 3470

East Asian (EAS) AF: 0.0883 AC: 457 AN: 5178

South Asian (SAS) AF: 0.202 AC: 975 AN: 4820

European-Finnish (FIN) AF: 0.108 AC: 1144 AN: 10562

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0789 AC: 5363 AN: 68000

Other (OTH) AF: 0.127 AC: 269 AN: 2110

Alfa AF: 0.127 Hom.: 646

Bravo AF: 0.158

Asia WGS AF: 0.169 AC: 584 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.34
DANN	Benign	0.57
PhyloP100		-0.95
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs16905599; hg19: chr9-22069144;