rs9358533

Variant names:

• chr6-22321775-C-T
• rs9358533
• ENST00000561912.3:n.705+3977C>T

Variant summary

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

The ENST00000561912.3(CASC15):​n.705+3977C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,048 control chromosomes in the GnomAD database, including 2,863 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 0.17 (2863 hom., cov: 32)
• Consequence: CASC15 ENST00000561912.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 5 publications found

Genes affected

CASC15 (HGNC:28245): (cancer susceptibility 15) This gene produces a long non-coding RNA that may regulate cell proliferation. This RNA is upregulated in hepatocellular carcinoma, where it is thought to function as an oncogene. However, some splice variants of this gene may function as a tumor suppressor in neuroblastoma and other tumor types. Circular RNA variants were observed at this gene. [provided by RefSeq, Dec 2017]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.312 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
CASC15	ENST00000561912.3	n.705+3977C>T		intron_variant	Intron 6 of 10	5
CASC15	ENST00000651569.1	n.641+3977C>T		intron_variant	Intron 6 of 7

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25141 AN: 151930 Hom.: 2845 Cov.: 32

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.0744

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.0435

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0910

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.166 AC: 25199 AN: 152048 Hom.: 2863 Cov.: 32 AF XY: 0.164 AC XY: 12205 AN XY: 74320

African (AFR) AF: 0.317 AC: 13127 AN: 41430

American (AMR) AF: 0.162 AC: 2466 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0744 AC: 258 AN: 3470

East Asian (EAS) AF: 0.269 AC: 1389 AN: 5154

South Asian (SAS) AF: 0.178 AC: 857 AN: 4810

European-Finnish (FIN) AF: 0.0435 AC: 461 AN: 10602

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.0910 AC: 6186 AN: 67998

Other (OTH) AF: 0.152 AC: 321 AN: 2112

Alfa AF: 0.119 Hom.: 4549

Bravo AF: 0.180

Asia WGS AF: 0.236 AC: 819 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.1
DANN	Benign	0.83
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs9358533; hg19: chr6-22322004;