rs3218020

Variant names:

• chr9-21997873-G-A
• rs3218020
• ENST00000428597.7:n.371+2712G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-21997873-G-A
• chr9-21997873-G-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+2712G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 151,848 control chromosomes in the GnomAD database, including 8,276 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 0.32 (8276 hom., cov: 31)
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.533
• 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]

ENSG00000264545 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.491 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN2B-AS1	NR_003529.4	MANE Select	n.371+2712G>A		intron	N/A
	CDKN2B-AS1	NR_047532.2		n.371+2712G>A		intron	N/A
	CDKN2B-AS1	NR_047533.2		n.371+2712G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.371+2712G>A		intron	N/A
	CDKN2B-AS1	ENST00000455933.8	TSL:1	n.340+2712G>A		intron	N/A
	CDKN2B-AS1	ENST00000577551.5	TSL:1	n.260+2712G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47970 AN: 151730 Hom.: 8284 Cov.: 31

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.370

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

GnomAD4 genome AF: 0.316 AC: 47963 AN: 151848 Hom.: 8276 Cov.: 31 AF XY: 0.318 AC XY: 23630 AN XY: 74208

African (AFR) AF: 0.174 AC: 7201 AN: 41408

American (AMR) AF: 0.361 AC: 5507 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.466 AC: 1617 AN: 3472

East Asian (EAS) AF: 0.508 AC: 2615 AN: 5152

South Asian (SAS) AF: 0.409 AC: 1962 AN: 4802

European-Finnish (FIN) AF: 0.366 AC: 3849 AN: 10516

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.352 AC: 23935 AN: 67922

Other (OTH) AF: 0.366 AC: 773 AN: 2114

Alfa AF: 0.329 Hom.: 5042

Bravo AF: 0.308

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.1
DANN	Benign	0.79
PhyloP100		0.53

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3218020;

hg19: chr9-21997872;