chr9-22082376-A-C

Variant names:

• chr9-22082376-A-C
• rs1547705
• ENST00000428597.7:n.2449-13996A>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.2449-13996A>C 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 152,204 control chromosomes in the GnomAD database, including 1,877 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 (1877 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00200
• Publications: 16 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.229 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.2449-13996A>C		intron	N/A
	CDKN2B-AS1	NR_047532.2		n.1076-9932A>C		intron	N/A
	CDKN2B-AS1	NR_047534.2		n.645-14882A>C		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.2449-13996A>C		intron	N/A
	CDKN2B-AS1	ENST00000577551.5	TSL:1	n.534-29944A>C		intron	N/A
	CDKN2B-AS1	ENST00000580576.6	TSL:1	n.1076-9932A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21828 AN: 152086 Hom.: 1876 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0412

Gnomad FIN AF: 0.0687

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.143 AC: 21840 AN: 152204 Hom.: 1877 Cov.: 32 AF XY: 0.137 AC XY: 10178 AN XY: 74416

African (AFR) AF: 0.233 AC: 9653 AN: 41500

American (AMR) AF: 0.135 AC: 2072 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 372 AN: 3470

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5178

South Asian (SAS) AF: 0.0412 AC: 199 AN: 4828

European-Finnish (FIN) AF: 0.0687 AC: 729 AN: 10604

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8283 AN: 68010

Other (OTH) AF: 0.149 AC: 314 AN: 2114

Alfa AF: 0.125 Hom.: 2598

Bravo AF: 0.156

Asia WGS AF: 0.0320 AC: 113 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.5
DANN	Benign	0.78
PhyloP100		0.0020

Splicing

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

Other links and lift over

dbSNP: rs1547705; hg19: chr9-22082375;