9-22009699-G-C

Variant names:

• chr9-22009699-G-C
• rs2069418
• ENST00000428597.7:n.371+14538G>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+14538G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.699 in 152,148 control chromosomes in the GnomAD database, including 39,198 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 0.70 (39198 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.322
• Publications: 36 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.914 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+14538G>C		intron	N/A
	CDKN2B-AS1	NR_047532.2		n.371+14538G>C		intron	N/A
	CDKN2B-AS1	NR_047533.2		n.371+14538G>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+14538G>C		intron	N/A
	CDKN2B-AS1	ENST00000455933.8	TSL:1	n.340+14538G>C		intron	N/A
	CDKN2B-AS1	ENST00000577551.5	TSL:1	n.260+14538G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.699 AC: 106214 AN: 152030 Hom.: 39140 Cov.: 32

Gnomad AFR AF: 0.921

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.769

Gnomad ASJ AF: 0.677

Gnomad EAS AF: 0.892

Gnomad SAS AF: 0.738

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.713

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

GnomAD4 genome AF: 0.699 AC: 106323 AN: 152148 Hom.: 39198 Cov.: 32 AF XY: 0.701 AC XY: 52127 AN XY: 74376

African (AFR) AF: 0.921 AC: 38266 AN: 41534

American (AMR) AF: 0.769 AC: 11760 AN: 15290

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

East Asian (EAS) AF: 0.892 AC: 4611 AN: 5172

South Asian (SAS) AF: 0.739 AC: 3560 AN: 4818

European-Finnish (FIN) AF: 0.566 AC: 5988 AN: 10576

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.554 AC: 37652 AN: 67976

Other (OTH) AF: 0.707 AC: 1492 AN: 2110

Alfa AF: 0.483 Hom.: 1374

Bravo AF: 0.722

Asia WGS AF: 0.786 AC: 2733 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.4
DANN	Benign	0.59
PhyloP100		0.32
PromoterAI		-0.023	Neutral

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: rs2069418; hg19: chr9-22009698; COSMIC: COSV52805437;