rs10965235

Variant names:

• chr9-22115106-C-A
• rs10965235
• ENST00000428597.7:n.2908+1307C>A

Variant summary

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

The ENST00000428597.7(CDKN2B-AS1):​n.2908+1307C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,084 control chromosomes in the GnomAD database, including 4,797 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 0.15 (4797 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.896
• Publications: 56 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 = 0.466 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.2908+1307C>A		intron	N/A
	CDKN2B-AS1	NR_047532.2		n.1697+1307C>A		intron	N/A
	CDKN2B-AS1	NR_047534.2		n.961+1307C>A		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.2908+1307C>A		intron	N/A
	CDKN2B-AS1	ENST00000422420.3	TSL:1	n.299+1307C>A		intron	N/A
	CDKN2B-AS1	ENST00000577551.5	TSL:1	n.609+2711C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22126 AN: 151966 Hom.: 4776 Cov.: 32

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0582

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.0693

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.00328

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.146 AC: 22200 AN: 152084 Hom.: 4797 Cov.: 32 AF XY: 0.142 AC XY: 10588 AN XY: 74352

African (AFR) AF: 0.472 AC: 19535 AN: 41412

American (AMR) AF: 0.0582 AC: 889 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0133 AC: 46 AN: 3468

East Asian (EAS) AF: 0.180 AC: 934 AN: 5176

South Asian (SAS) AF: 0.0693 AC: 334 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.00328 AC: 223 AN: 68014

Other (OTH) AF: 0.106 AC: 224 AN: 2110

Alfa AF: 0.0491 Hom.: 6151

Bravo AF: 0.166

Asia WGS AF: 0.117 AC: 404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.19
DANN	Benign	0.53
PhyloP100		-0.90

Splicing

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

Other links and lift over

dbSNP: rs10965235; hg19: chr9-22115105;