6-22283656-C-T

Variant names:

• chr6-22283656-C-T
• rs849870
• ENST00000561912.3:n.459-7222C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.93).
• 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000561912.3	n.459-7222C>T		intron_variant	Intron 3 of 10	5
CASC15	ENST00000651569.1	n.376-7203C>T		intron_variant	Intron 3 of 7

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

African (AFR) AF: 0.328 AC: 13575 AN: 41430

American (AMR) AF: 0.158 AC: 2421 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 581 AN: 3468

East Asian (EAS) AF: 0.0396 AC: 205 AN: 5182

South Asian (SAS) AF: 0.235 AC: 1131 AN: 4816

European-Finnish (FIN) AF: 0.164 AC: 1732 AN: 10574

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9334 AN: 67976

Other (OTH) AF: 0.189 AC: 400 AN: 2112

Alfa AF: 0.167 Hom.: 858

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
PhyloP100		-1.1

Splicing

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

Other links and lift over

dbSNP: rs849870; hg19: chr6-22283885;