ENST00000561912.3:n.200-9999C>T

Variant names:

• chr6-22246375-C-T
• rs4236016
• ENST00000561912.3:n.200-9999C>T

Variant summary

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

The ENST00000561912.3(CASC15):​n.200-9999C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.988 in 152,092 control chromosomes in the GnomAD database, including 74,243 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 0.99 (74243 hom., cov: 29)
• Consequence: CASC15 ENST00000561912.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 12 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000561912.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

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

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC15	ENST00000561912.3	TSL:5	n.200-9999C>T		intron	N/A
	CASC15	ENST00000651569.1		n.116+9558C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.988 AC: 150149 AN: 151974 Hom.: 74189 Cov.: 29

Gnomad AFR AF: 0.959

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.994

Gnomad ASJ AF: 0.999

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.997

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.992

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

GnomAD4 genome AF: 0.988 AC: 150262 AN: 152092 Hom.: 74243 Cov.: 29 AF XY: 0.988 AC XY: 73464 AN XY: 74332

African (AFR) AF: 0.959 AC: 39753 AN: 41462

American (AMR) AF: 0.994 AC: 15197 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.999 AC: 3469 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5144 AN: 5144

South Asian (SAS) AF: 1.00 AC: 4802 AN: 4802

European-Finnish (FIN) AF: 1.00 AC: 10586 AN: 10586

Middle Eastern (MID) AF: 0.997 AC: 293 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68011 AN: 68026

Other (OTH) AF: 0.992 AC: 2095 AN: 2112

Alfa AF: 0.995 Hom.: 125254

Bravo AF: 0.986

Asia WGS AF: 0.995 AC: 3458 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.063
DANN	Benign	0.56
PhyloP100		-1.0

Splicing

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

Other links and lift over

dbSNP: rs4236016; hg19: chr6-22246604;