chr9-22097023-C-T

Variant names:

• chr9-22097023-C-T
• rs16905644
• ENST00000428597.7:n.2592-235C>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.2592-235C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0419 in 152,248 control chromosomes in the GnomAD database, including 306 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 0.042 (306 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.880
• Publications: 4 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 = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN2B-AS1	NR_003529.4	n.2592-235C>T		intron_variant	Intron 13 of 18
CDKN2B-AS1	NR_047532.2	n.1381-235C>T		intron_variant	Intron 8 of 13
CDKN2B-AS1	NR_047534.2	n.645-235C>T		intron_variant	Intron 3 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000428597.7	n.2592-235C>T		intron_variant	Intron 13 of 18	1
CDKN2B-AS1	ENST00000577551.5	n.534-15297C>T		intron_variant	Intron 3 of 6	1
CDKN2B-AS1	ENST00000580576.6	n.1381-235C>T		intron_variant	Intron 8 of 13	1

Frequencies

GnomAD3 genomes AF: 0.0418 AC: 6354 AN: 152130 Hom.: 302 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0307

Gnomad ASJ AF: 0.0242

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0240

Gnomad FIN AF: 0.00745

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0102

Gnomad OTH AF: 0.0402

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

GnomAD4 genome AF: 0.0419 AC: 6379 AN: 152248 Hom.: 306 Cov.: 32 AF XY: 0.0419 AC XY: 3119 AN XY: 74436

African (AFR) AF: 0.116 AC: 4837 AN: 41524

American (AMR) AF: 0.0307 AC: 469 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0242 AC: 84 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.0240 AC: 116 AN: 4826

European-Finnish (FIN) AF: 0.00745 AC: 79 AN: 10602

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0102 AC: 696 AN: 68024

Other (OTH) AF: 0.0393 AC: 83 AN: 2112

Alfa AF: 0.0161 Hom.: 21

Bravo AF: 0.0465

Asia WGS AF: 0.0160 AC: 57 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.9
DANN	Benign	0.67
PhyloP100		0.88
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs16905644; hg19: chr9-22097022;