rs9368373

Positions:

• chr6-21916421-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_015410.2(CASC15):​n.781+6818T>C 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 0.422 in 151,566 control chromosomes in the GnomAD database, including 13,564 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 0.42 (13564 hom., cov: 30)
• Consequence: CASC15 NR_015410.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.169

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASC15	NR_015410.2	n.781+6818T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASC15	ENST00000688254.1	n.684+6818T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.422 AC: 63927 AN: 151452 Hom.: 13556 Cov.: 30

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.601

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.416

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

GnomAD4 genome AF: 0.422 AC: 63957 AN: 151566 Hom.: 13564 Cov.: 30 AF XY: 0.424 AC XY: 31437 AN XY: 74078

Gnomad4 AFR AF: 0.405

Gnomad4 AMR AF: 0.377

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.601

Gnomad4 SAS AF: 0.470

Gnomad4 FIN AF: 0.416

Gnomad4 NFE AF: 0.425

Gnomad4 OTH AF: 0.418

Alfa AF: 0.427 Hom.: 9578

Bravo AF: 0.412

Asia WGS AF: 0.521 AC: 1814 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.7
DANN	Benign	0.54

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9368373; hg19: chr6-21916652;