ENST00000428597.7:n.2449-8898T>C

Variant names:

• chr9-22087474-T-C
• rs7857345
• ENST00000428597.7:n.2449-8898T>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.2449-8898T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.79 in 152,190 control chromosomes in the GnomAD database, including 48,439 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 0.79 (48439 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.311
• Publications: 24 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN2B-AS1	NR_003529.4	n.2449-8898T>C		intron_variant	Intron 12 of 18
CDKN2B-AS1	NR_047532.2	n.1076-4834T>C		intron_variant	Intron 6 of 13
CDKN2B-AS1	NR_047534.2	n.645-9784T>C		intron_variant	Intron 3 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000428597.7	n.2449-8898T>C		intron_variant	Intron 12 of 18	1
CDKN2B-AS1	ENST00000577551.5	n.534-24846T>C		intron_variant	Intron 3 of 6	1
CDKN2B-AS1	ENST00000580576.6	n.1076-4834T>C		intron_variant	Intron 6 of 13	1

Frequencies

GnomAD3 genomes AF: 0.790 AC: 120118 AN: 152072 Hom.: 48377 Cov.: 32

Gnomad AFR AF: 0.942

Gnomad AMI AF: 0.769

Gnomad AMR AF: 0.863

Gnomad ASJ AF: 0.819

Gnomad EAS AF: 0.680

Gnomad SAS AF: 0.776

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.712

Gnomad OTH AF: 0.822

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

GnomAD4 genome AF: 0.790 AC: 120239 AN: 152190 Hom.: 48439 Cov.: 32 AF XY: 0.786 AC XY: 58449 AN XY: 74404

African (AFR) AF: 0.942 AC: 39155 AN: 41550

American (AMR) AF: 0.863 AC: 13204 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.819 AC: 2842 AN: 3472

East Asian (EAS) AF: 0.681 AC: 3513 AN: 5162

South Asian (SAS) AF: 0.777 AC: 3758 AN: 4834

European-Finnish (FIN) AF: 0.634 AC: 6705 AN: 10570

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.712 AC: 48371 AN: 67984

Other (OTH) AF: 0.818 AC: 1727 AN: 2112

Alfa AF: 0.768 Hom.: 27144

Bravo AF: 0.813

Asia WGS AF: 0.736 AC: 2559 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.4
DANN	Benign	0.75
PhyloP100		-0.31

Splicing

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

Other links and lift over

dbSNP: rs7857345; hg19: chr9-22087473;