rs7865618

Variant names:

• chr9-22031006-G-A
• rs7865618
• ENST00000428597.7:n.533+1412G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-22031006-G-A
• chr9-22031006-G-C
• chr9-22031006-G-T

Variant summary

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

The ENST00000428597.7(CDKN2B-AS1):​n.533+1412G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.715 in 152,090 control chromosomes in the GnomAD database, including 40,758 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 0.72 (40758 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580
• Publications: 122 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN2B-AS1	NR_003529.4	n.533+1412G>A		intron_variant	Intron 2 of 18	ENST00000428597.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000428597.7	n.533+1412G>A		intron_variant	Intron 2 of 18	1	NR_003529.4

Frequencies

GnomAD3 genomes AF: 0.715 AC: 108664 AN: 151972 Hom.: 40701 Cov.: 32

Gnomad AFR AF: 0.926

Gnomad AMI AF: 0.527

Gnomad AMR AF: 0.785

Gnomad ASJ AF: 0.717

Gnomad EAS AF: 0.892

Gnomad SAS AF: 0.746

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.732

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.715 AC: 108774 AN: 152090 Hom.: 40758 Cov.: 32 AF XY: 0.716 AC XY: 53264 AN XY: 74342

African (AFR) AF: 0.926 AC: 38464 AN: 41548

American (AMR) AF: 0.785 AC: 11982 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.717 AC: 2484 AN: 3464

East Asian (EAS) AF: 0.891 AC: 4609 AN: 5170

South Asian (SAS) AF: 0.747 AC: 3603 AN: 4826

European-Finnish (FIN) AF: 0.585 AC: 6184 AN: 10562

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.577 AC: 39182 AN: 67932

Other (OTH) AF: 0.727 AC: 1538 AN: 2116

Alfa AF: 0.625 Hom.: 112524

Bravo AF: 0.738

Asia WGS AF: 0.795 AC: 2758 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.5
DANN	Benign	0.78
PhyloP100		0.058

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: rs7865618; hg19: chr9-22031005;