9-22077544-C-T

Variant names:

• chr9-22077544-C-T
• rs1412832
• ENST00000428597.7:n.2448+11191C>T

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+11191C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.778 in 152,114 control chromosomes in the GnomAD database, including 47,106 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 0.78 (47106 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.171
• Publications: 38 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.939 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.2448+11191C>T		intron	N/A
	CDKN2B-AS1	NR_047532.2		n.1076-14764C>T		intron	N/A
	CDKN2B-AS1	NR_047533.2		n.645-135C>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.2448+11191C>T		intron	N/A
	CDKN2B-AS1	ENST00000455933.8	TSL:1	n.750-135C>T		intron	N/A
	CDKN2B-AS1	ENST00000577551.5	TSL:1	n.533+28316C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.777 AC: 118165 AN: 151996 Hom.: 47045 Cov.: 32

Gnomad AFR AF: 0.947

Gnomad AMI AF: 0.696

Gnomad AMR AF: 0.851

Gnomad ASJ AF: 0.810

Gnomad EAS AF: 0.707

Gnomad SAS AF: 0.779

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.805

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

GnomAD4 genome AF: 0.778 AC: 118281 AN: 152114 Hom.: 47106 Cov.: 32 AF XY: 0.772 AC XY: 57426 AN XY: 74342

African (AFR) AF: 0.947 AC: 39333 AN: 41536

American (AMR) AF: 0.852 AC: 13027 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.810 AC: 2813 AN: 3472

East Asian (EAS) AF: 0.707 AC: 3643 AN: 5154

South Asian (SAS) AF: 0.779 AC: 3757 AN: 4820

European-Finnish (FIN) AF: 0.593 AC: 6251 AN: 10536

Middle Eastern (MID) AF: 0.878 AC: 258 AN: 294

European-Non Finnish (NFE) AF: 0.690 AC: 46874 AN: 67980

Other (OTH) AF: 0.800 AC: 1690 AN: 2112

Alfa AF: 0.720 Hom.: 105176

Bravo AF: 0.803

Asia WGS AF: 0.757 AC: 2627 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.2
DANN	Benign	0.47
PhyloP100		-0.17

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: rs1412832;

hg19: chr9-22077543;