rs10965219

Variant names:

• chr9-22053688-A-G
• rs10965219
• ENST00000428597.7:n.1253-2564A>G

Your query was ambiguous. Multiple possible variants found:

• chr9-22053688-A-G
• chr9-22053688-A-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.1253-2564A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 152,066 control chromosomes in the GnomAD database, including 26,901 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 0.58 (26901 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.189
• Publications: 24 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN2B-AS1	NR_003529.4	n.1253-2564A>G		intron_variant	Intron 6 of 18
CDKN2B-AS1	NR_047532.2	n.940-2564A>G		intron_variant	Intron 5 of 13
CDKN2B-AS1	NR_047533.2	n.644+4460A>G		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000428597.7	n.1253-2564A>G		intron_variant	Intron 6 of 18	1
CDKN2B-AS1	ENST00000455933.8	n.614-2564A>G		intron_variant	Intron 3 of 4	1
CDKN2B-AS1	ENST00000577551.5	n.533+4460A>G		intron_variant	Intron 3 of 6	1

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88796 AN: 151948 Hom.: 26870 Cov.: 32

Gnomad AFR AF: 0.704

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.642

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.616

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

GnomAD4 genome AF: 0.584 AC: 88878 AN: 152066 Hom.: 26901 Cov.: 32 AF XY: 0.586 AC XY: 43579 AN XY: 74310

African (AFR) AF: 0.704 AC: 29191 AN: 41464

American (AMR) AF: 0.695 AC: 10614 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.613 AC: 2126 AN: 3470

East Asian (EAS) AF: 0.694 AC: 3587 AN: 5166

South Asian (SAS) AF: 0.641 AC: 3094 AN: 4824

European-Finnish (FIN) AF: 0.503 AC: 5313 AN: 10564

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.486 AC: 33008 AN: 67984

Other (OTH) AF: 0.611 AC: 1290 AN: 2110

Alfa AF: 0.567 Hom.: 16151

Bravo AF: 0.605

Asia WGS AF: 0.666 AC: 2314 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.72
PhyloP100		0.19

Splicing

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

Other links and lift over

dbSNP: rs10965219; hg19: chr9-22053687;