rs12199382

Positions:

• chr6-22326901-G-A
• chr6-22326901-G-T

Variant summary

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

The ENST00000561912.3(CASC15):​n.705+9103G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 151,958 control chromosomes in the GnomAD database, including 8,655 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 (8655 hom., cov: 33)
• Consequence: CASC15 ENST00000561912.3 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000561912.3	n.705+9103G>A		intron_variant, non_coding_transcript_variant		5
CASC15	ENST00000651569.1	n.641+9103G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46264 AN: 151840 Hom.: 8653 Cov.: 33

Gnomad AFR AF: 0.0821

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.327

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

GnomAD4 genome AF: 0.305 AC: 46282 AN: 151958 Hom.: 8655 Cov.: 33 AF XY: 0.309 AC XY: 22913 AN XY: 74266

Gnomad4 AFR AF: 0.0819

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.355

Gnomad4 EAS AF: 0.385

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.452

Gnomad4 NFE AF: 0.406

Gnomad4 OTH AF: 0.328

Alfa AF: 0.233 Hom.: 932

Bravo AF: 0.285

Asia WGS AF: 0.285 AC: 992 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	0.094
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12199382; hg19: chr6-22327130;