rs9368373

Variant names:

• chr6-21916421-T-C
• rs9368373
• ENST00000444265.6:n.199+6818T>C

Variant summary

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

The ENST00000444265.6(CASC15):​n.199+6818T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 151,566 control chromosomes in the GnomAD database, including 13,564 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 (13564 hom., cov: 30)
• Consequence: CASC15 ENST00000444265.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.169
• Publications: 2 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000444265.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC15	NR_015410.2		n.781+6818T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC15	ENST00000444265.6	TSL:1	n.199+6818T>C		intron	N/A
	CASC15	ENST00000606851.5	TSL:2	n.750+6818T>C		intron	N/A
	CASC15	ENST00000607048.5	TSL:2	n.376+6818T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.422 AC: 63927 AN: 151452 Hom.: 13556 Cov.: 30

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.601

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.416

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

GnomAD4 genome AF: 0.422 AC: 63957 AN: 151566 Hom.: 13564 Cov.: 30 AF XY: 0.424 AC XY: 31437 AN XY: 74078

African (AFR) AF: 0.405 AC: 16666 AN: 41130

American (AMR) AF: 0.377 AC: 5736 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1519 AN: 3464

East Asian (EAS) AF: 0.601 AC: 3098 AN: 5154

South Asian (SAS) AF: 0.470 AC: 2262 AN: 4810

European-Finnish (FIN) AF: 0.416 AC: 4373 AN: 10508

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.425 AC: 28896 AN: 67956

Other (OTH) AF: 0.418 AC: 880 AN: 2104

Alfa AF: 0.427 Hom.: 13034

Bravo AF: 0.412

Asia WGS AF: 0.521 AC: 1814 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.7
DANN	Benign	0.54
PhyloP100		-0.17

Splicing

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

Other links and lift over

dbSNP: rs9368373; hg19: chr6-21916652;