ENST00000606336.5:n.843+8233C>A

Variant names:

• chr6-21766767-C-A
• rs9466179
• ENST00000606336.5:n.843+8233C>A

Variant summary

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

The ENST00000606336.5(CASC15):​n.843+8233C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 152,060 control chromosomes in the GnomAD database, including 7,542 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 (7542 hom., cov: 32)
• Consequence: CASC15 ENST00000606336.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC15	NR_015410.2	n.487-16865C>A		intron_variant	Intron 2 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000606336.5	n.843+8233C>A		intron_variant	Intron 5 of 6	1
CASC15	ENST00000606851.5	n.456-16865C>A		intron_variant	Intron 2 of 11	2
CASC15	ENST00000607048.5	n.82-16865C>A		intron_variant	Intron 1 of 11	2

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43715 AN: 151942 Hom.: 7518 Cov.: 32

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.278

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

GnomAD4 genome AF: 0.288 AC: 43781 AN: 152060 Hom.: 7542 Cov.: 32 AF XY: 0.286 AC XY: 21229 AN XY: 74324

African (AFR) AF: 0.463 AC: 19171 AN: 41432

American (AMR) AF: 0.346 AC: 5280 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 513 AN: 3470

East Asian (EAS) AF: 0.449 AC: 2313 AN: 5150

South Asian (SAS) AF: 0.205 AC: 989 AN: 4822

European-Finnish (FIN) AF: 0.147 AC: 1551 AN: 10584

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13072 AN: 68006

Other (OTH) AF: 0.276 AC: 581 AN: 2108

Alfa AF: 0.224 Hom.: 14172

Bravo AF: 0.313

Asia WGS AF: 0.316 AC: 1098 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.060
DANN	Benign	0.60
PhyloP100		-1.6

Splicing

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

Other links and lift over

dbSNP: rs9466179; hg19: chr6-21766998;