9-22010005-T-A

Variant names:

• chr9-22010005-T-A
• rs2069416
• ENST00000428597.7:n.371+14844T>A

Variant summary

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

The ENST00000428597.7(CDKN2B-AS1):​n.371+14844T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 152,054 control chromosomes in the GnomAD database, including 8,076 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 0.31 (8076 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.230
• Publications: 15 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]

ENSG00000264545 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.564 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.371+14844T>A		intron	N/A
	CDKN2B-AS1	NR_047532.2		n.371+14844T>A		intron	N/A
	CDKN2B-AS1	NR_047533.2		n.371+14844T>A		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.371+14844T>A		intron	N/A
	CDKN2B-AS1	ENST00000455933.8	TSL:1	n.340+14844T>A		intron	N/A
	CDKN2B-AS1	ENST00000577551.5	TSL:1	n.260+14844T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47319 AN: 151936 Hom.: 8089 Cov.: 32

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.353

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

GnomAD4 genome AF: 0.311 AC: 47306 AN: 152054 Hom.: 8076 Cov.: 32 AF XY: 0.314 AC XY: 23335 AN XY: 74300

African (AFR) AF: 0.176 AC: 7298 AN: 41496

American (AMR) AF: 0.353 AC: 5395 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1452 AN: 3466

East Asian (EAS) AF: 0.581 AC: 3004 AN: 5168

South Asian (SAS) AF: 0.414 AC: 1992 AN: 4816

European-Finnish (FIN) AF: 0.337 AC: 3550 AN: 10536

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.345 AC: 23422 AN: 67978

Other (OTH) AF: 0.349 AC: 737 AN: 2110

Alfa AF: 0.180 Hom.: 379

Bravo AF: 0.310

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	6.0
DANN	Benign	0.85
PhyloP100		-0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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: rs2069416;

hg19: chr9-22010004;