6-22310963-T-C

Variant names:

• chr6-22310963-T-C
• rs9393273
• ENST00000561912.3:n.570-5864T>C

Variant summary

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

The ENST00000561912.3(CASC15):​n.570-5864T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,006 control chromosomes in the GnomAD database, including 7,745 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 0.29 (7745 hom., cov: 32)
• Consequence: CASC15 ENST00000561912.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0370
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.384 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.570-5864T>C		intron_variant	Intron 4 of 10	5
CASC15	ENST00000651569.1	n.506-5864T>C		intron_variant	Intron 4 of 7

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43962 AN: 151886 Hom.: 7748 Cov.: 32

Gnomad AFR AF: 0.0864

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.315

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

GnomAD4 genome AF: 0.289 AC: 43970 AN: 152006 Hom.: 7745 Cov.: 32 AF XY: 0.291 AC XY: 21600 AN XY: 74334

African (AFR) AF: 0.0862 AC: 3578 AN: 41508

American (AMR) AF: 0.307 AC: 4693 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1274 AN: 3470

East Asian (EAS) AF: 0.384 AC: 1982 AN: 5164

South Asian (SAS) AF: 0.210 AC: 1017 AN: 4832

European-Finnish (FIN) AF: 0.377 AC: 3958 AN: 10502

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.388 AC: 26378 AN: 67938

Other (OTH) AF: 0.316 AC: 667 AN: 2108

Alfa AF: 0.315 Hom.: 1118

Bravo AF: 0.278

Asia WGS AF: 0.267 AC: 926 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.3
DANN	Benign	0.75
PhyloP100		0.037

Splicing

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

Other links and lift over

dbSNP: rs9393273; hg19: chr6-22311192;