rs1156546

Positions:

• chr6-22308463-A-C
• chr6-22308463-A-G

Variant summary

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

The ENST00000561912.3(CASC15):​n.570-8364A>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 0.298 in 151,974 control chromosomes in the GnomAD database, including 7,778 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 0.30 (7778 hom., cov: 32)
• Consequence: CASC15 ENST00000561912.3 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.673

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.458 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.570-8364A>C		intron_variant, non_coding_transcript_variant		5
CASC15	ENST00000651569.1	n.506-8364A>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45247 AN: 151858 Hom.: 7747 Cov.: 32

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.295

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

GnomAD4 genome AF: 0.298 AC: 45326 AN: 151974 Hom.: 7778 Cov.: 32 AF XY: 0.299 AC XY: 22218 AN XY: 74296

Gnomad4 AFR AF: 0.464

Gnomad4 AMR AF: 0.326

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.391

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.206

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.298

Alfa AF: 0.259 Hom.: 761

Bravo AF: 0.312

Asia WGS AF: 0.380 AC: 1316 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.52
DANN	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1156546; hg19: chr6-22308692;