9-22033367-C-T

Variant names:

• chr9-22033367-C-T
• rs2157719
• ENST00000428597.7:n.846+381C>T

Variant summary

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

The ENST00000652420.1(CDKN2B-AS1):​n.1042C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.715 in 152,062 control chromosomes in the GnomAD database, including 40,791 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 0.72 (40791 hom., cov: 31)
• Consequence: CDKN2B-AS1 ENST00000652420.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.363
• Publications: 120 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 (AFR) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000652420.1. 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
	CDKN2B-AS1	NR_003529.4	MANE Select	n.846+381C>T		intron	N/A
	CDKN2B-AS1	NR_047532.2		n.533+3773C>T		intron	N/A
	CDKN2B-AS1	NR_047533.2		n.372-13384C>T		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.846+381C>T		intron	N/A
	CDKN2B-AS1	ENST00000455933.8	TSL:1	n.341-13384C>T		intron	N/A
	CDKN2B-AS1	ENST00000577551.5	TSL:1	n.261-13384C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.715 AC: 108688 AN: 151944 Hom.: 40734 Cov.: 31

Gnomad AFR AF: 0.926

Gnomad AMI AF: 0.527

Gnomad AMR AF: 0.785

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.891

Gnomad SAS AF: 0.748

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.734

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

GnomAD4 genome AF: 0.715 AC: 108798 AN: 152062 Hom.: 40791 Cov.: 31 AF XY: 0.717 AC XY: 53276 AN XY: 74306

African (AFR) AF: 0.926 AC: 38463 AN: 41542

American (AMR) AF: 0.785 AC: 11975 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.718 AC: 2489 AN: 3468

East Asian (EAS) AF: 0.891 AC: 4589 AN: 5150

South Asian (SAS) AF: 0.748 AC: 3609 AN: 4822

European-Finnish (FIN) AF: 0.588 AC: 6203 AN: 10554

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.577 AC: 39207 AN: 67954

Other (OTH) AF: 0.728 AC: 1537 AN: 2110

Alfa AF: 0.620 Hom.: 108877

Bravo AF: 0.738

Asia WGS AF: 0.793 AC: 2756 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	4.6
DANN	Benign	0.62
PhyloP100		0.36

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: rs2157719;

hg19: chr9-22033366;