6-22348660-T-G

Variant names:

• chr6-22348660-T-G
• rs12524161
• ENST00000561912.3:n.992-569T>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000561912.3(CASC15):​n.992-569T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 152,014 control chromosomes in the GnomAD database, including 8,213 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 (8213 hom., cov: 30)
• Consequence: CASC15 ENST00000561912.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.981

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.39 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.992-569T>G		intron_variant	Intron 8 of 10	5

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44979 AN: 151896 Hom.: 8214 Cov.: 30

Gnomad AFR AF: 0.0762

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.301

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

GnomAD4 genome AF: 0.296 AC: 44990 AN: 152014 Hom.: 8213 Cov.: 30 AF XY: 0.300 AC XY: 22265 AN XY: 74280

Gnomad4 AFR AF: 0.0760

Gnomad4 AMR AF: 0.315

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.386

Gnomad4 SAS AF: 0.261

Gnomad4 FIN AF: 0.440

Gnomad4 NFE AF: 0.394

Gnomad4 OTH AF: 0.302

Alfa AF: 0.214 Hom.: 572

Bravo AF: 0.278

Asia WGS AF: 0.281 AC: 976 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.89
DANN	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12524161; hg19: chr6-22348889;