chr6-22308463-A-C

Variant names:

• chr6-22308463-A-C
• rs1156546
• ENST00000561912.3:n.570-8364A>C

Variant summary

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

The ENST00000561912.3(CASC15):​n.570-8364A>C variant causes a intron 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.673
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.458 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC15	ENST00000561912.3	TSL:5	n.570-8364A>C		intron	N/A
	CASC15	ENST00000651569.1		n.506-8364A>C		intron	N/A

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

African (AFR) AF: 0.464 AC: 19200 AN: 41390

American (AMR) AF: 0.326 AC: 4973 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 742 AN: 3472

East Asian (EAS) AF: 0.391 AC: 2023 AN: 5170

South Asian (SAS) AF: 0.321 AC: 1543 AN: 4812

European-Finnish (FIN) AF: 0.206 AC: 2172 AN: 10566

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13746 AN: 67976

Other (OTH) AF: 0.298 AC: 629 AN: 2110

Alfa AF: 0.251 Hom.: 1442

Bravo AF: 0.312

Asia WGS AF: 0.380 AC: 1316 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.52
DANN	Benign	0.71
PhyloP100		-0.67

Splicing

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

Other links and lift over

dbSNP: rs1156546; hg19: chr6-22308692;