rs9366427

Positions:

• chr6-22096384-C-G
• chr6-22096384-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000444265.6(CASC15):​n.888-14363C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 151,734 control chromosomes in the GnomAD database, including 17,585 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 0.47 (17585 hom., cov: 30)
• Consequence: CASC15 ENST00000444265.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASC15	NR_015410.2	n.1249-14363C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000444265.6	n.888-14363C>G		intron_variant		1
CASC15	ENST00000606851.5	n.1218-14363C>G		intron_variant		2
CASC15	ENST00000607048.5	n.844-14363C>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71130 AN: 151618 Hom.: 17577 Cov.: 30

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.701

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.454

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

GnomAD4 genome AF: 0.469 AC: 71148 AN: 151734 Hom.: 17585 Cov.: 30 AF XY: 0.466 AC XY: 34526 AN XY: 74146

Gnomad4 AFR AF: 0.383

Gnomad4 AMR AF: 0.377

Gnomad4 ASJ AF: 0.437

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.405

Gnomad4 FIN AF: 0.616

Gnomad4 NFE AF: 0.547

Gnomad4 OTH AF: 0.448

Alfa AF: 0.492 Hom.: 2254

Bravo AF: 0.446

Asia WGS AF: 0.265 AC: 923 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.93
DANN	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9366427; hg19: chr6-22096613;