rs993600

Variant names:

• chr6-22045415-A-G
• rs993600
• ENST00000444265.6:n.522-11131A>G

Variant summary

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

The ENST00000444265.6(CASC15):​n.522-11131A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,010 control chromosomes in the GnomAD database, including 2,663 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 0.18 (2663 hom., cov: 31)
• Consequence: CASC15 ENST00000444265.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.915
• Publications: 3 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=-0.24).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC15	NR_015410.2	n.1104-11131A>G		intron_variant	Intron 7 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000444265.6	n.522-11131A>G		intron_variant	Intron 4 of 10	1
CASC15	ENST00000606851.5	n.1073-11131A>G		intron_variant	Intron 7 of 11	2
CASC15	ENST00000607048.5	n.699-11131A>G		intron_variant	Intron 6 of 11	2

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27994 AN: 151892 Hom.: 2653 Cov.: 31

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.164

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

GnomAD4 genome AF: 0.184 AC: 28031 AN: 152010 Hom.: 2663 Cov.: 31 AF XY: 0.190 AC XY: 14106 AN XY: 74276

African (AFR) AF: 0.158 AC: 6570 AN: 41466

American (AMR) AF: 0.195 AC: 2975 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 376 AN: 3468

East Asian (EAS) AF: 0.224 AC: 1152 AN: 5150

South Asian (SAS) AF: 0.230 AC: 1111 AN: 4828

European-Finnish (FIN) AF: 0.263 AC: 2775 AN: 10538

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12537 AN: 67982

Other (OTH) AF: 0.171 AC: 360 AN: 2110

Alfa AF: 0.182 Hom.: 4844

Bravo AF: 0.177

Asia WGS AF: 0.252 AC: 875 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	11
DANN	Benign	0.91
PhyloP100		0.92

Splicing

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

Other links and lift over

dbSNP: rs993600; hg19: chr6-22045644;