9-22084311-C-T

Variant names:

• chr9-22084311-C-T
• rs1537370
• ENST00000428597.6:n.2449-12061C>T

Variant summary

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

The ENST00000428597.6(CDKN2B-AS1):​n.2449-12061C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 152,012 control chromosomes in the GnomAD database, including 24,168 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 0.56 (24168 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000428597.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.338

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN2B-AS1	NR_003529.4	n.2449-12061C>T		intron_variant	Intron 12 of 18
CDKN2B-AS1	NR_047532.2	n.1076-7997C>T		intron_variant	Intron 6 of 13
CDKN2B-AS1	NR_047534.2	n.645-12947C>T		intron_variant	Intron 3 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000428597.6	n.2449-12061C>T		intron_variant	Intron 12 of 18	1
CDKN2B-AS1	ENST00000577551.5	n.534-28009C>T		intron_variant	Intron 3 of 6	1
CDKN2B-AS1	ENST00000580576.6	n.1076-7997C>T		intron_variant	Intron 6 of 13	1

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84445 AN: 151890 Hom.: 24151 Cov.: 32

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.611

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.587

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

GnomAD4 genome AF: 0.556 AC: 84516 AN: 152012 Hom.: 24168 Cov.: 32 AF XY: 0.551 AC XY: 40880 AN XY: 74256

Gnomad4 AFR AF: 0.681

Gnomad4 AMR AF: 0.523

Gnomad4 ASJ AF: 0.635

Gnomad4 EAS AF: 0.695

Gnomad4 SAS AF: 0.610

Gnomad4 FIN AF: 0.413

Gnomad4 NFE AF: 0.490

Gnomad4 OTH AF: 0.584

Alfa AF: 0.514 Hom.: 22712

Bravo AF: 0.566

Asia WGS AF: 0.626 AC: 2177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.8
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1537370; hg19: chr9-22084310;