ENST00000444265.6:n.887+10185G>A

Variant names:

• chr6-22073425-G-A
• rs10484390
• ENST00000444265.6:n.887+10185G>A

Variant summary

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

The ENST00000444265.6(CASC15):​n.887+10185G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,112 control chromosomes in the GnomAD database, including 2,325 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 0.11 (2325 hom., cov: 32)
• Consequence: CASC15 ENST00000444265.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.00
• 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 (EAS) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC15	NR_015410.2	n.1248+16735G>A		intron_variant	Intron 8 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000444265.6	n.887+10185G>A		intron_variant	Intron 6 of 10	1
CASC15	ENST00000606851.5	n.1217+16735G>A		intron_variant	Intron 8 of 11	2
CASC15	ENST00000607048.5	n.843+16735G>A		intron_variant	Intron 7 of 11	2

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16315 AN: 151994 Hom.: 2325 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.0314

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.0741

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0102

Gnomad OTH AF: 0.0927

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

GnomAD4 genome AF: 0.107 AC: 16343 AN: 152112 Hom.: 2325 Cov.: 32 AF XY: 0.117 AC XY: 8696 AN XY: 74356

African (AFR) AF: 0.173 AC: 7192 AN: 41468

American (AMR) AF: 0.213 AC: 3251 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0314 AC: 109 AN: 3470

East Asian (EAS) AF: 0.649 AC: 3350 AN: 5164

South Asian (SAS) AF: 0.156 AC: 751 AN: 4808

European-Finnish (FIN) AF: 0.0741 AC: 784 AN: 10578

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0102 AC: 691 AN: 68014

Other (OTH) AF: 0.0927 AC: 196 AN: 2114

Alfa AF: 0.0506 Hom.: 4106

Bravo AF: 0.126

Asia WGS AF: 0.305 AC: 1058 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	0.032
DANN	Benign	0.49
PhyloP100		-3.0

Splicing

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

Other links and lift over

dbSNP: rs10484390; hg19: chr6-22073654;