9-22057531-A-C

Variant names:

• chr9-22057531-A-C
• rs77728904
• ENST00000428597.7:n.1389-828A>C

Variant summary

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

The ENST00000428597.7(CDKN2B-AS1):​n.1389-828A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0759 in 152,270 control chromosomes in the GnomAD database, including 439 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 0.076 (439 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.630
• Publications: 11 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN2B-AS1	NR_003529.4	n.1389-828A>C		intron_variant	Intron 7 of 18
CDKN2B-AS1	NR_047532.2	n.1075+1144A>C		intron_variant	Intron 6 of 13
CDKN2B-AS1	NR_047533.2	n.644+8303A>C		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000428597.7	n.1389-828A>C		intron_variant	Intron 7 of 18	1
CDKN2B-AS1	ENST00000455933.8	n.749+1144A>C		intron_variant	Intron 4 of 4	1
CDKN2B-AS1	ENST00000577551.5	n.533+8303A>C		intron_variant	Intron 3 of 6	1

Frequencies

GnomAD3 genomes AF: 0.0759 AC: 11543 AN: 152152 Hom.: 438 Cov.: 32

Gnomad AFR AF: 0.0924

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0602

Gnomad ASJ AF: 0.0808

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0366

Gnomad FIN AF: 0.0759

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0781

Gnomad OTH AF: 0.0760

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

GnomAD4 genome AF: 0.0759 AC: 11558 AN: 152270 Hom.: 439 Cov.: 32 AF XY: 0.0745 AC XY: 5550 AN XY: 74476

African (AFR) AF: 0.0925 AC: 3845 AN: 41562

American (AMR) AF: 0.0601 AC: 919 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0808 AC: 280 AN: 3466

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5186

South Asian (SAS) AF: 0.0369 AC: 178 AN: 4830

European-Finnish (FIN) AF: 0.0759 AC: 805 AN: 10610

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0781 AC: 5310 AN: 68010

Other (OTH) AF: 0.0752 AC: 159 AN: 2114

Alfa AF: 0.0592 Hom.: 96

Bravo AF: 0.0743

Asia WGS AF: 0.0310 AC: 109 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	2.7
DANN	Benign	0.72
PhyloP100		0.63

Splicing

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

Other links and lift over

dbSNP: rs77728904; hg19: chr9-22057530;