9-22153361-A-G

Variant names:

• chr9-22153361-A-G
• rs7853123
• ENST00000755351.1:n.302+25959A>G

Variant summary

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

The ENST00000755351.1(CDKN2B-AS1):​n.302+25959A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 151,968 control chromosomes in the GnomAD database, including 32,610 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 0.64 (32610 hom., cov: 31)
• Consequence: CDKN2B-AS1 ENST00000755351.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.333
• Publications: 5 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.947 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000755351.1	n.302+25959A>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97372 AN: 151850 Hom.: 32558 Cov.: 31

Gnomad AFR AF: 0.799

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.678

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.970

Gnomad SAS AF: 0.719

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.606

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

GnomAD4 genome AF: 0.641 AC: 97480 AN: 151968 Hom.: 32610 Cov.: 31 AF XY: 0.647 AC XY: 48030 AN XY: 74258

African (AFR) AF: 0.799 AC: 33145 AN: 41460

American (AMR) AF: 0.678 AC: 10357 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 1716 AN: 3464

East Asian (EAS) AF: 0.970 AC: 5024 AN: 5182

South Asian (SAS) AF: 0.720 AC: 3461 AN: 4808

European-Finnish (FIN) AF: 0.569 AC: 5983 AN: 10522

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.530 AC: 36041 AN: 67946

Other (OTH) AF: 0.607 AC: 1283 AN: 2112

Alfa AF: 0.557 Hom.: 36376

Bravo AF: 0.657

Asia WGS AF: 0.838 AC: 2914 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.19
DANN	Benign	0.69
PhyloP100		-0.33

Splicing

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

Other links and lift over

dbSNP: rs7853123; hg19: chr9-22153360;