9-22074794-T-C

Variant names:

• chr9-22074794-T-C
• rs7855162
• ENST00000428597.7:n.2448+8441T>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.2448+8441T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,196 control chromosomes in the GnomAD database, including 2,783 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 0.12 (2783 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 9 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.351 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.2448+8441T>C		intron	N/A
	CDKN2B-AS1	NR_047532.2		n.1076-17514T>C		intron	N/A
	CDKN2B-AS1	NR_047533.2		n.645-2885T>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.2448+8441T>C		intron	N/A
	CDKN2B-AS1	ENST00000455933.8	TSL:1	n.750-2885T>C		intron	N/A
	CDKN2B-AS1	ENST00000577551.5	TSL:1	n.533+25566T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17878 AN: 152078 Hom.: 2774 Cov.: 32

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0612

Gnomad ASJ AF: 0.0262

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.0775

Gnomad FIN AF: 0.00696

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.00881

Gnomad OTH AF: 0.0937

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

GnomAD4 genome AF: 0.118 AC: 17928 AN: 152196 Hom.: 2783 Cov.: 32 AF XY: 0.116 AC XY: 8609 AN XY: 74432

African (AFR) AF: 0.356 AC: 14744 AN: 41466

American (AMR) AF: 0.0611 AC: 935 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0262 AC: 91 AN: 3470

East Asian (EAS) AF: 0.173 AC: 894 AN: 5176

South Asian (SAS) AF: 0.0779 AC: 376 AN: 4824

European-Finnish (FIN) AF: 0.00696 AC: 74 AN: 10628

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.00881 AC: 599 AN: 68018

Other (OTH) AF: 0.0937 AC: 198 AN: 2114

Alfa AF: 0.0435 Hom.: 3424

Bravo AF: 0.133

Asia WGS AF: 0.113 AC: 393 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.8
DANN	Benign	0.68
PhyloP100		-1.1

Splicing

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

Other links and lift over

dbSNP: rs7855162; hg19: chr9-22074793;