rs575427

Variant names:

• chr9-22011478-A-G
• rs575427
• ENST00000428597.6:n.371+16317A>G

Variant summary

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

The ENST00000428597.6(CDKN2B-AS1):​n.371+16317A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0668 in 152,276 control chromosomes in the GnomAD database, including 461 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 0.067 (461 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000428597.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.748

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]

ENSG00000264545 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0983 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN2B-AS1	NR_003529.4	n.371+16317A>G		intron_variant	Intron 1 of 18
CDKN2B-AS1	NR_047532.2	n.371+16317A>G		intron_variant	Intron 1 of 13
CDKN2B-AS1	NR_047533.2	n.371+16317A>G		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000428597.6	n.371+16317A>G		intron_variant	Intron 1 of 18	1
CDKN2B-AS1	ENST00000455933.7	n.340+16317A>G		intron_variant	Intron 1 of 4	1
CDKN2B-AS1	ENST00000577551.5	n.260+16317A>G		intron_variant	Intron 1 of 6	1

Frequencies

GnomAD3 genomes AF: 0.0668 AC: 10168 AN: 152158 Hom.: 461 Cov.: 32

Gnomad AFR AF: 0.0180

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.0576

Gnomad ASJ AF: 0.0957

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0296

Gnomad FIN AF: 0.0765

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.0779

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

GnomAD4 genome AF: 0.0668 AC: 10170 AN: 152276 Hom.: 461 Cov.: 32 AF XY: 0.0652 AC XY: 4853 AN XY: 74456

Gnomad4 AFR AF: 0.0180

Gnomad4 AMR AF: 0.0576

Gnomad4 ASJ AF: 0.0957

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0299

Gnomad4 FIN AF: 0.0765

Gnomad4 NFE AF: 0.100

Gnomad4 OTH AF: 0.0785

Alfa AF: 0.0836 Hom.: 144

Bravo AF: 0.0644

Asia WGS AF: 0.0310 AC: 106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	6.8
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs575427; hg19: chr9-22011477;