rs849870

Positions:

• chr6-22283656-C-T

Variant summary

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

The ENST00000561912.3(CASC15):​n.459-7222C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,050 control chromosomes in the GnomAD database, including 3,446 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 0.19 (3446 hom., cov: 32)
• Consequence: CASC15 ENST00000561912.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000561912.3	n.459-7222C>T		intron_variant		5
CASC15	ENST00000651569.1	n.376-7203C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29422 AN: 151932 Hom.: 3436 Cov.: 32

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.0395

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.194 AC: 29477 AN: 152050 Hom.: 3446 Cov.: 32 AF XY: 0.194 AC XY: 14388 AN XY: 74318

Gnomad4 AFR AF: 0.328

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.0396

Gnomad4 SAS AF: 0.235

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.189

Alfa AF: 0.177 Hom.: 509

Bravo AF: 0.195

Asia WGS AF: 0.154 AC: 535 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.16
DANN	Benign	0.27

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs849870; hg19: chr6-22283885;