rs1537375

Variant names:

• chr9-22116072-T-C
• rs1537375
• ENST00000428597.7:n.2908+2273T>C

Your query was ambiguous. Multiple possible variants found:

• chr9-22116072-T-C
• chr9-22116072-T-G

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+2273T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 152,046 control chromosomes in the GnomAD database, including 25,465 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 0.57 (25465 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.135
• 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=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.681 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+2273T>C		intron	N/A
	CDKN2B-AS1	NR_047532.2		n.1697+2273T>C		intron	N/A
	CDKN2B-AS1	NR_047534.2		n.961+2273T>C		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+2273T>C		intron	N/A
	CDKN2B-AS1	ENST00000422420.3	TSL:1	n.299+2273T>C		intron	N/A
	CDKN2B-AS1	ENST00000577551.5	TSL:1	n.610-2572T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.573 AC: 86998 AN: 151928 Hom.: 25444 Cov.: 32

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.670

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.602

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

GnomAD4 genome AF: 0.573 AC: 87076 AN: 152046 Hom.: 25465 Cov.: 32 AF XY: 0.566 AC XY: 42066 AN XY: 74318

African (AFR) AF: 0.688 AC: 28522 AN: 41482

American (AMR) AF: 0.568 AC: 8672 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.652 AC: 2261 AN: 3468

East Asian (EAS) AF: 0.670 AC: 3449 AN: 5146

South Asian (SAS) AF: 0.599 AC: 2888 AN: 4820

European-Finnish (FIN) AF: 0.424 AC: 4486 AN: 10568

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.513 AC: 34876 AN: 67966

Other (OTH) AF: 0.598 AC: 1265 AN: 2114

Alfa AF: 0.514 Hom.: 17101

Bravo AF: 0.587

Asia WGS AF: 0.613 AC: 2128 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	8.1
DANN	Benign	0.91
PhyloP100		0.14

Splicing

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

Other links and lift over

dbSNP: rs1537375; hg19: chr9-22116071;