9-22088095-A-G

Variant names:

• chr9-22088095-A-G
• rs10738607
• ENST00000428597.7:n.2449-8277A>G

Variant summary

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

The ENST00000428597.7(CDKN2B-AS1):​n.2449-8277A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 151,508 control chromosomes in the GnomAD database, including 14,836 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 0.43 (14836 hom., cov: 31)
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.877
• Publications: 38 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN2B-AS1	NR_003529.4	n.2449-8277A>G		intron_variant	Intron 12 of 18
CDKN2B-AS1	NR_047532.2	n.1076-4213A>G		intron_variant	Intron 6 of 13
CDKN2B-AS1	NR_047534.2	n.645-9163A>G		intron_variant	Intron 3 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000428597.7	n.2449-8277A>G		intron_variant	Intron 12 of 18	1
CDKN2B-AS1	ENST00000577551.5	n.534-24225A>G		intron_variant	Intron 3 of 6	1
CDKN2B-AS1	ENST00000580576.6	n.1076-4213A>G		intron_variant	Intron 6 of 13	1

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64419 AN: 151390 Hom.: 14852 Cov.: 31

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.650

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.425 AC: 64425 AN: 151508 Hom.: 14836 Cov.: 31 AF XY: 0.422 AC XY: 31236 AN XY: 74018

African (AFR) AF: 0.235 AC: 9711 AN: 41384

American (AMR) AF: 0.461 AC: 7010 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.621 AC: 2150 AN: 3460

East Asian (EAS) AF: 0.664 AC: 3396 AN: 5114

South Asian (SAS) AF: 0.585 AC: 2811 AN: 4802

European-Finnish (FIN) AF: 0.403 AC: 4234 AN: 10496

Middle Eastern (MID) AF: 0.634 AC: 185 AN: 292

European-Non Finnish (NFE) AF: 0.494 AC: 33467 AN: 67750

Other (OTH) AF: 0.484 AC: 1016 AN: 2098

Alfa AF: 0.431 Hom.: 9590

Bravo AF: 0.420

Asia WGS AF: 0.571 AC: 1985 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.87
DANN	Benign	0.51
PhyloP100		-0.88

Splicing

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

Other links and lift over

dbSNP: rs10738607; hg19: chr9-22088094;