rs993600

chr6-22045415-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NR_015410.2(CASC15):n.1104-11131A>G variant causes a intron, non coding transcript 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 NR_015410.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.915

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 -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/exons	MANE	UniProt
CASC15	NR_015410.2	n.1104-11131A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASC15	ENST00000688254.1	n.1007-11131A>G		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.195

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.224

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.263

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.171

Alfa AF: 0.180 Hom.: 3608

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs993600; hg19: chr6-22045644;