9-22134095-T-C

Variant names:

• chr9-22134095-T-C
• rs10811661
• ENST00000755351.1:n.302+6693T>C

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+6693T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,226 control chromosomes in the GnomAD database, including 2,053 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 0.15 (2053 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000755351.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.989
• Publications: 552 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000755351.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN2B-AS1	ENST00000755351.1		n.302+6693T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22215 AN: 152108 Hom.: 2054 Cov.: 32

Gnomad AFR AF: 0.0666

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.146 AC: 22211 AN: 152226 Hom.: 2053 Cov.: 32 AF XY: 0.147 AC XY: 10923 AN XY: 74424

African (AFR) AF: 0.0664 AC: 2761 AN: 41558

American (AMR) AF: 0.158 AC: 2420 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 558 AN: 3472

East Asian (EAS) AF: 0.413 AC: 2133 AN: 5162

South Asian (SAS) AF: 0.143 AC: 692 AN: 4832

European-Finnish (FIN) AF: 0.143 AC: 1516 AN: 10602

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11604 AN: 67992

Other (OTH) AF: 0.160 AC: 338 AN: 2112

Alfa AF: 0.167 Hom.: 7241

Bravo AF: 0.146

Asia WGS AF: 0.286 AC: 995 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.2
DANN	Benign	0.58
PhyloP100		0.99

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10811661;

hg19: chr9-22134094;