chr6-21785940-C-T

Variant names:

• chr6-21785940-C-T
• rs9466182
• ENST00000606336.5:n.920+2232C>T

Variant summary

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

The ENST00000606336.5(CASC15):​n.920+2232C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 151,878 control chromosomes in the GnomAD database, including 2,909 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 (2909 hom., cov: 32)
• Consequence: CASC15 ENST00000606336.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.404
• Publications: 7 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 = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC15	NR_015410.2	n.563+2232C>T		intron_variant	Intron 3 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000606336.5	n.920+2232C>T		intron_variant	Intron 6 of 6	1
CASC15	ENST00000606851.5	n.532+2232C>T		intron_variant	Intron 3 of 11	2
CASC15	ENST00000607048.5	n.158+2232C>T		intron_variant	Intron 2 of 11	2

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28178 AN: 151762 Hom.: 2906 Cov.: 32

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0644

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.173

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

GnomAD4 genome AF: 0.186 AC: 28202 AN: 151878 Hom.: 2909 Cov.: 32 AF XY: 0.179 AC XY: 13264 AN XY: 74208

African (AFR) AF: 0.255 AC: 10543 AN: 41380

American (AMR) AF: 0.140 AC: 2131 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 569 AN: 3468

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5172

South Asian (SAS) AF: 0.0644 AC: 310 AN: 4812

European-Finnish (FIN) AF: 0.156 AC: 1640 AN: 10516

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12381 AN: 67966

Other (OTH) AF: 0.173 AC: 364 AN: 2110

Alfa AF: 0.181 Hom.: 8365

Bravo AF: 0.189

Asia WGS AF: 0.0440 AC: 155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.40
PhyloP100		-0.40

Splicing

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

Other links and lift over

dbSNP: rs9466182; hg19: chr6-21786171;