chr6-22096384-C-G

Variant names:

• chr6-22096384-C-G
• rs9366427
• ENST00000444265.6:n.888-14363C>G

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.92).
• 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 rank	MANE	Protein	UniProt
CASC15	NR_015410.2	n.1249-14363C>G		intron_variant	Intron 8 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000444265.6	n.888-14363C>G		intron_variant	Intron 6 of 10	1
CASC15	ENST00000606851.5	n.1218-14363C>G		intron_variant	Intron 8 of 11	2
CASC15	ENST00000607048.5	n.844-14363C>G		intron_variant	Intron 7 of 11	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

African (AFR) AF: 0.383 AC: 15852 AN: 41356

American (AMR) AF: 0.377 AC: 5743 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 1513 AN: 3466

East Asian (EAS) AF: 0.139 AC: 717 AN: 5162

South Asian (SAS) AF: 0.405 AC: 1947 AN: 4804

European-Finnish (FIN) AF: 0.616 AC: 6471 AN: 10510

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.547 AC: 37159 AN: 67890

Other (OTH) AF: 0.448 AC: 943 AN: 2106

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
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs9366427; hg19: chr6-22096613;