rs1123886

Positions:

• chr6-22267746-T-C
• chr6-22267746-T-G

Variant summary

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

The ENST00000561912.3(CASC15):​n.458+7248T>C 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 0.33 in 152,110 control chromosomes in the GnomAD database, including 9,221 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 0.33 (9221 hom., cov: 32)
• Consequence: CASC15 ENST00000561912.3 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.363

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.411 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.458+7248T>C		intron_variant, non_coding_transcript_variant		5
CASC15	ENST00000651569.1	n.375+7248T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50205 AN: 151992 Hom.: 9216 Cov.: 32

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.0472

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.330 AC: 50221 AN: 152110 Hom.: 9221 Cov.: 32 AF XY: 0.326 AC XY: 24249 AN XY: 74370

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.272

Gnomad4 ASJ AF: 0.379

Gnomad4 EAS AF: 0.0473

Gnomad4 SAS AF: 0.335

Gnomad4 FIN AF: 0.430

Gnomad4 NFE AF: 0.415

Gnomad4 OTH AF: 0.323

Alfa AF: 0.342 Hom.: 3289

Bravo AF: 0.312

Asia WGS AF: 0.195 AC: 677 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.46

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1123886; hg19: chr6-22267975;