9-22041444-T-C

Variant names:

• chr9-22041444-T-C
• rs1360590
• ENST00000428597.7:n.847-4873T>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.847-4873T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.59 in 151,906 control chromosomes in the GnomAD database, including 27,584 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 0.59 (27584 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 21 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.729 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.847-4873T>C		intron	N/A
	CDKN2B-AS1	NR_047532.2		n.534-4873T>C		intron	N/A
	CDKN2B-AS1	NR_047533.2		n.372-5307T>C		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.847-4873T>C		intron	N/A
	CDKN2B-AS1	ENST00000455933.8	TSL:1	n.341-5307T>C		intron	N/A
	CDKN2B-AS1	ENST00000577551.5	TSL:1	n.261-5307T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89485 AN: 151788 Hom.: 27550 Cov.: 32

Gnomad AFR AF: 0.735

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.694

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.662

Gnomad NFE AF: 0.479

Gnomad OTH AF: 0.619

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

GnomAD4 genome AF: 0.590 AC: 89571 AN: 151906 Hom.: 27584 Cov.: 32 AF XY: 0.592 AC XY: 43939 AN XY: 74242

African (AFR) AF: 0.735 AC: 30486 AN: 41450

American (AMR) AF: 0.692 AC: 10559 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 2129 AN: 3468

East Asian (EAS) AF: 0.694 AC: 3572 AN: 5150

South Asian (SAS) AF: 0.646 AC: 3112 AN: 4820

European-Finnish (FIN) AF: 0.495 AC: 5227 AN: 10558

Middle Eastern (MID) AF: 0.668 AC: 195 AN: 292

European-Non Finnish (NFE) AF: 0.479 AC: 32542 AN: 67902

Other (OTH) AF: 0.613 AC: 1292 AN: 2106

Alfa AF: 0.513 Hom.: 12037

Bravo AF: 0.612

Asia WGS AF: 0.669 AC: 2326 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.36
DANN	Benign	0.80
PhyloP100		-1.1

Splicing

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

Other links and lift over

dbSNP: rs1360590; hg19: chr9-22041443;