rs9393231

Variant names:

• chr6-22123466-A-C
• rs9393231
• ENST00000444265.6:n.1061+12546A>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000444265.6(CASC15):​n.1061+12546A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 151,842 control chromosomes in the GnomAD database, including 21,087 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 0.52 (21087 hom., cov: 30)
• Consequence: CASC15 ENST00000444265.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.433
• Publications: 5 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC15	NR_015410.2	n.1422+12546A>C		intron_variant	Intron 9 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000444265.6	n.1061+12546A>C		intron_variant	Intron 7 of 10	1
CASC15	ENST00000606851.5	n.1391+12546A>C		intron_variant	Intron 9 of 11	2
CASC15	ENST00000607048.5	n.1138+9429A>C		intron_variant	Intron 9 of 11	2

Frequencies

GnomAD3 genomes AF: 0.520 AC: 78823 AN: 151722 Hom.: 21079 Cov.: 30

Gnomad AFR AF: 0.592

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.500

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.586

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.518

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

GnomAD4 genome AF: 0.519 AC: 78859 AN: 151842 Hom.: 21087 Cov.: 30 AF XY: 0.517 AC XY: 38334 AN XY: 74198

African (AFR) AF: 0.592 AC: 24487 AN: 41382

American (AMR) AF: 0.472 AC: 7195 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.484 AC: 1680 AN: 3470

East Asian (EAS) AF: 0.194 AC: 1002 AN: 5166

South Asian (SAS) AF: 0.499 AC: 2404 AN: 4820

European-Finnish (FIN) AF: 0.556 AC: 5852 AN: 10522

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.508 AC: 34511 AN: 67912

Other (OTH) AF: 0.513 AC: 1081 AN: 2106

Alfa AF: 0.510 Hom.: 32546

Bravo AF: 0.513

Asia WGS AF: 0.388 AC: 1351 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	9.9
DANN	Benign	0.83
PhyloP100		0.43

Splicing

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

Other links and lift over

dbSNP: rs9393231; hg19: chr6-22123695;