rs12193939

Variant names:

• chr6-22564923-G-A
• rs12193939
• ENST00000652081.2:n.146-9196G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000652081.2(CASC15):​n.146-9196G>A variant causes a intron 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 ENST00000652081.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000652081.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC15	ENST00000652081.2		n.146-9196G>A		intron	N/A
	CASC15	ENST00000846434.1		n.433-9196G>A		intron	N/A

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

African (AFR) AF: 0.144 AC: 5980 AN: 41512

American (AMR) AF: 0.266 AC: 4051 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 512 AN: 3466

East Asian (EAS) AF: 0.375 AC: 1931 AN: 5148

South Asian (SAS) AF: 0.307 AC: 1480 AN: 4824

European-Finnish (FIN) AF: 0.164 AC: 1737 AN: 10592

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.159 AC: 10773 AN: 67962

Other (OTH) AF: 0.184 AC: 389 AN: 2112

Alfa AF: 0.169 Hom.: 4120

Bravo AF: 0.183

Asia WGS AF: 0.339 AC: 1176 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.66
DANN	Benign	0.84
PhyloP100		-0.0050

Splicing

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

Other links and lift over

dbSNP: rs12193939; hg19: chr6-22565152;