rs10738610

Variant names:

• chr9-22123767-A-C
• rs10738610
• ENST00000650946.1:n.439-3336A>C

Your query was ambiguous. Multiple possible variants found:

• chr9-22123767-A-C
• chr9-22123767-A-T

Variant summary

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

The ENST00000650946.1(CDKN2B-AS1):​n.439-3336A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 151,980 control chromosomes in the GnomAD database, including 14,772 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 0.42 (14772 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000650946.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16
• Publications: 34 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN2B-AS1	NR_185859.1	n.781-3336A>C		intron_variant	Intron 4 of 4
CDKN2B-AS1	NR_185867.1	n.1256-3336A>C		intron_variant	Intron 6 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000650946.1	n.439-3336A>C		intron_variant	Intron 4 of 4

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63462 AN: 151862 Hom.: 14786 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.491

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

GnomAD4 genome AF: 0.418 AC: 63461 AN: 151980 Hom.: 14772 Cov.: 32 AF XY: 0.414 AC XY: 30764 AN XY: 74256

African (AFR) AF: 0.201 AC: 8336 AN: 41518

American (AMR) AF: 0.503 AC: 7674 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.626 AC: 2170 AN: 3466

East Asian (EAS) AF: 0.508 AC: 2620 AN: 5154

South Asian (SAS) AF: 0.531 AC: 2550 AN: 4806

European-Finnish (FIN) AF: 0.414 AC: 4365 AN: 10542

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.502 AC: 34080 AN: 67916

Other (OTH) AF: 0.487 AC: 1027 AN: 2110

Alfa AF: 0.376 Hom.: 5735

Bravo AF: 0.412

Asia WGS AF: 0.500 AC: 1740 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.9
DANN	Benign	0.71
PhyloP100		1.2

Splicing

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

Other links and lift over

dbSNP: rs10738610; hg19: chr9-22123766;