rs10733376

Positions:

• chr9-22114470-G-C

Variant summary

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

The ENST00000422420.2(CDKN2B-AS1):​n.134+671G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 152,106 control chromosomes in the GnomAD database, including 33,238 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 0.64 (33238 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000422420.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.180

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDKN2B-AS1	NR_003529.4	n.2908+671G>C		intron_variant
CDKN2B-AS1	NR_047532.2	n.1697+671G>C		intron_variant
CDKN2B-AS1	NR_047534.2	n.961+671G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000422420.2	n.134+671G>C		intron_variant		1
CDKN2B-AS1	ENST00000428597.6	n.2908+671G>C		intron_variant		1
CDKN2B-AS1	ENST00000577551.5	n.609+2075G>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.640 AC: 97223 AN: 151988 Hom.: 33193 Cov.: 32

Gnomad AFR AF: 0.895

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.675

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.623

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.662

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

GnomAD4 genome AF: 0.640 AC: 97325 AN: 152106 Hom.: 33238 Cov.: 32 AF XY: 0.631 AC XY: 46952 AN XY: 74360

Gnomad4 AFR AF: 0.896

Gnomad4 AMR AF: 0.611

Gnomad4 ASJ AF: 0.675

Gnomad4 EAS AF: 0.628

Gnomad4 SAS AF: 0.621

Gnomad4 FIN AF: 0.431

Gnomad4 NFE AF: 0.524

Gnomad4 OTH AF: 0.657

Alfa AF: 0.579 Hom.: 3368

Bravo AF: 0.661

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	-0.95
CADD	Benign	0.76
DANN	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10733376; hg19: chr9-22114469;