9-22074794-T-C

Variant names:

• chr9-22074794-T-C
• rs7855162
• ENST00000428597.6:n.2448+8441T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000428597.6(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 ENST00000428597.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN2B-AS1	NR_003529.4	n.2448+8441T>C		intron_variant	Intron 12 of 18
CDKN2B-AS1	NR_047532.2	n.1076-17514T>C		intron_variant	Intron 6 of 13
CDKN2B-AS1	NR_047533.2	n.645-2885T>C		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000428597.6	n.2448+8441T>C		intron_variant	Intron 12 of 18	1
CDKN2B-AS1	ENST00000455933.7	n.750-2885T>C		intron_variant	Intron 4 of 4	1
CDKN2B-AS1	ENST00000577551.5	n.533+25566T>C		intron_variant	Intron 3 of 6	1

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

Gnomad4 AFR AF: 0.356

Gnomad4 AMR AF: 0.0611

Gnomad4 ASJ AF: 0.0262

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.0779

Gnomad4 FIN AF: 0.00696

Gnomad4 NFE AF: 0.00881

Gnomad4 OTH AF: 0.0937

Alfa AF: 0.0278 Hom.: 784

Bravo AF: 0.133

Asia WGS AF: 0.113 AC: 393 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7855162; hg19: chr9-22074793;