9-22206988-C-T

Variant names:

• chr9-22206988-C-T
• rs1679013
• ENST00000435092.2:n.374-2929G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000435092.2(ENSG00000236921):​n.374-2929G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 152,018 control chromosomes in the GnomAD database, including 15,889 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 0.44 (15889 hom., cov: 32)
• Consequence: ENSG00000236921 ENST00000435092.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.84
• Publications: 30 publications found

Genes affected

ENSG00000236921 (HGNC:):

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000236921	ENST00000435092.2	n.374-2929G>A		intron_variant	Intron 3 of 3	3
CDKN2B-AS1	ENST00000755351.1	n.303-3676C>T		intron_variant	Intron 1 of 1
ENSG00000236921	ENST00000755459.1	n.319-2929G>A		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67312 AN: 151902 Hom.: 15899 Cov.: 32

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.790

Gnomad SAS AF: 0.638

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.485

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

GnomAD4 genome AF: 0.443 AC: 67314 AN: 152018 Hom.: 15889 Cov.: 32 AF XY: 0.447 AC XY: 33246 AN XY: 74302

African (AFR) AF: 0.313 AC: 12948 AN: 41428

American (AMR) AF: 0.433 AC: 6618 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.621 AC: 2154 AN: 3468

East Asian (EAS) AF: 0.790 AC: 4093 AN: 5180

South Asian (SAS) AF: 0.637 AC: 3073 AN: 4822

European-Finnish (FIN) AF: 0.437 AC: 4611 AN: 10554

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.475 AC: 32311 AN: 67964

Other (OTH) AF: 0.485 AC: 1023 AN: 2108

Alfa AF: 0.469 Hom.: 48675

Bravo AF: 0.438

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	20
DANN	Benign	0.87
PhyloP100		2.8

Splicing

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

Other links and lift over

dbSNP: rs1679013; hg19: chr9-22206987;