9-22043927-A-G

Variant names:

• chr9-22043927-A-G
• rs1412829
• ENST00000428597.7:n.847-2390A>G

Variant summary

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

The ENST00000428597.7(CDKN2B-AS1):​n.847-2390A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 151,872 control chromosomes in the GnomAD database, including 7,702 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 0.28 (7702 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.908
• Publications: 117 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.41 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN2B-AS1	NR_003529.4	MANE Select	n.847-2390A>G		intron	N/A
	CDKN2B-AS1	NR_047532.2		n.534-2390A>G		intron	N/A
	CDKN2B-AS1	NR_047533.2		n.372-2824A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.847-2390A>G		intron	N/A
	CDKN2B-AS1	ENST00000455933.8	TSL:1	n.341-2824A>G		intron	N/A
	CDKN2B-AS1	ENST00000577551.5	TSL:1	n.261-2824A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42429 AN: 151754 Hom.: 7696 Cov.: 32

Gnomad AFR AF: 0.0723

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.260

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

GnomAD4 genome AF: 0.279 AC: 42435 AN: 151872 Hom.: 7702 Cov.: 32 AF XY: 0.279 AC XY: 20675 AN XY: 74206

African (AFR) AF: 0.0721 AC: 2993 AN: 41512

American (AMR) AF: 0.213 AC: 3248 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 968 AN: 3464

East Asian (EAS) AF: 0.109 AC: 562 AN: 5166

South Asian (SAS) AF: 0.241 AC: 1164 AN: 4826

European-Finnish (FIN) AF: 0.418 AC: 4409 AN: 10544

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.414 AC: 28077 AN: 67820

Other (OTH) AF: 0.265 AC: 559 AN: 2108

Alfa AF: 0.370 Hom.: 44502

Bravo AF: 0.256

Asia WGS AF: 0.204 AC: 711 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.32
DANN	Benign	0.55
PhyloP100		-0.91

Splicing

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

Other links and lift over

dbSNP: rs1412829; hg19: chr9-22043926;