rs9460668

Variant names:

• chr6-21727698-C-G
• rs9460668
• ENST00000606336.5:n.576-15219C>G

Variant summary

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

The ENST00000606336.5(CASC15):​n.576-15219C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,160 control chromosomes in the GnomAD database, including 2,790 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 0.19 (2790 hom., cov: 32)
• Consequence: CASC15 ENST00000606336.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.979
• Publications: 1 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC15	NR_015410.2	n.487-55934C>G		intron_variant	Intron 2 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000606336.5	n.576-15219C>G		intron_variant	Intron 3 of 6	1
CASC15	ENST00000606851.5	n.456-55934C>G		intron_variant	Intron 2 of 11	2
CASC15	ENST00000607048.5	n.82-55934C>G		intron_variant	Intron 1 of 11	2

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28154 AN: 152042 Hom.: 2790 Cov.: 32

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.185 AC: 28158 AN: 152160 Hom.: 2790 Cov.: 32 AF XY: 0.179 AC XY: 13348 AN XY: 74384

African (AFR) AF: 0.225 AC: 9348 AN: 41512

American (AMR) AF: 0.142 AC: 2163 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 728 AN: 3470

East Asian (EAS) AF: 0.00289 AC: 15 AN: 5182

South Asian (SAS) AF: 0.109 AC: 525 AN: 4830

European-Finnish (FIN) AF: 0.146 AC: 1541 AN: 10580

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.193 AC: 13130 AN: 67982

Other (OTH) AF: 0.177 AC: 373 AN: 2112

Alfa AF: 0.187 Hom.: 340

Bravo AF: 0.187

Asia WGS AF: 0.0630 AC: 221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.88
DANN	Benign	0.48
PhyloP100		-0.98

Splicing

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

Other links and lift over

dbSNP: rs9460668; hg19: chr6-21727929;