rs1537374

Variant names:

• chr9-22116047-A-G
• rs1537374
• ENST00000422420.3:n.299+2248A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000422420.3(CDKN2B-AS1):​n.299+2248A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 152,116 control chromosomes in the GnomAD database, including 33,518 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 (33518 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000422420.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• Publications: 27 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN2B-AS1	NR_003529.4	n.2908+2248A>G		intron_variant	Intron 16 of 18
CDKN2B-AS1	NR_047532.2	n.1697+2248A>G		intron_variant	Intron 11 of 13
CDKN2B-AS1	NR_047534.2	n.961+2248A>G		intron_variant	Intron 6 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000422420.3	n.299+2248A>G		intron_variant	Intron 1 of 2	1
CDKN2B-AS1	ENST00000428597.7	n.2908+2248A>G		intron_variant	Intron 16 of 18	1
CDKN2B-AS1	ENST00000577551.5	n.610-2597A>G		intron_variant	Intron 4 of 6	1

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97610 AN: 151998 Hom.: 33474 Cov.: 32

Gnomad AFR AF: 0.898

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.677

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.625

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.665

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

GnomAD4 genome AF: 0.642 AC: 97711 AN: 152116 Hom.: 33518 Cov.: 32 AF XY: 0.634 AC XY: 47139 AN XY: 74330

African (AFR) AF: 0.898 AC: 37316 AN: 41564

American (AMR) AF: 0.612 AC: 9332 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.677 AC: 2347 AN: 3468

East Asian (EAS) AF: 0.671 AC: 3463 AN: 5158

South Asian (SAS) AF: 0.623 AC: 3004 AN: 4820

European-Finnish (FIN) AF: 0.432 AC: 4560 AN: 10550

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.524 AC: 35617 AN: 67974

Other (OTH) AF: 0.661 AC: 1398 AN: 2116

Alfa AF: 0.610 Hom.: 16967

Bravo AF: 0.664

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.12
DANN	Benign	0.67
PhyloP100		-1.3

Splicing

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

Other links and lift over

dbSNP: rs1537374; hg19: chr9-22116046;