chr9-22000248-T-C

Variant names:

• chr9-22000248-T-C
• rs3218005
• ENST00000428597.7:n.371+5087T>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.371+5087T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,104 control chromosomes in the GnomAD database, including 1,773 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 0.14 (1773 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.237
• Publications: 20 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]

ENSG00000264545 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000428597.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN2B-AS1	NR_003529.4	MANE Select	n.371+5087T>C		intron	N/A
	CDKN2B-AS1	NR_047532.2		n.371+5087T>C		intron	N/A
	CDKN2B-AS1	NR_047533.2		n.371+5087T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.371+5087T>C		intron	N/A
	CDKN2B-AS1	ENST00000455933.8	TSL:1	n.340+5087T>C		intron	N/A
	CDKN2B-AS1	ENST00000577551.5	TSL:1	n.260+5087T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21256 AN: 151986 Hom.: 1765 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.0242

Gnomad AMR AF: 0.0980

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.0832

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.140 AC: 21298 AN: 152104 Hom.: 1773 Cov.: 32 AF XY: 0.139 AC XY: 10338 AN XY: 74382

African (AFR) AF: 0.235 AC: 9738 AN: 41490

American (AMR) AF: 0.0978 AC: 1496 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 382 AN: 3468

East Asian (EAS) AF: 0.216 AC: 1117 AN: 5180

South Asian (SAS) AF: 0.113 AC: 544 AN: 4814

European-Finnish (FIN) AF: 0.0832 AC: 882 AN: 10598

Middle Eastern (MID) AF: 0.164 AC: 48 AN: 292

European-Non Finnish (NFE) AF: 0.100 AC: 6795 AN: 67950

Other (OTH) AF: 0.130 AC: 274 AN: 2112

Alfa AF: 0.110 Hom.: 1197

Bravo AF: 0.143

Asia WGS AF: 0.144 AC: 501 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.1
DANN	Benign	0.60
PhyloP100		0.24

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

Other links and lift over

dbSNP: rs3218005; hg19: chr9-22000247;