rs12193939

Positions:

• chr6-22564923-G-A

Variant summary

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

The ENST00000652081.1(CASC15):​n.146-9196G>A 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 0.178 in 152,080 control chromosomes in the GnomAD database, including 2,773 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 (2773 hom., cov: 32)
• Consequence: CASC15 ENST00000652081.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500

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]

LOC105374971 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC105374971	XR_001744025.1	n.489-9196G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASC15	ENST00000652081.1	n.146-9196G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27088 AN: 151962 Hom.: 2759 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.178 AC: 27126 AN: 152080 Hom.: 2773 Cov.: 32 AF XY: 0.184 AC XY: 13666 AN XY: 74334

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.266

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.375

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.184

Alfa AF: 0.169 Hom.: 3267

Bravo AF: 0.183

Asia WGS AF: 0.339 AC: 1176 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.66
DANN	Benign	0.84

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12193939; hg19: chr6-22565152;