rs1205918

chr6-22365533-A-G

Variant summary

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

The XR_001744024.2(LOC105374971):n.367+12882A>G 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 0.177 in 152,170 control chromosomes in the GnomAD database, including 3,793 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 0.18 (3793 hom., cov: 33)
• Consequence: LOC105374971 XR_001744024.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54

Genes affected

LOC105374971 (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC105374971	XR_001744024.2	n.367+12882A>G		intron_variant, non_coding_transcript_variant
LOC105374971	XR_001744023.2	n.368-2681A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASC15	ENST00000561912.3	n.1348-2681A>G		intron_variant, non_coding_transcript_variant		5
CASC15	ENST00000652081.1	n.145+12882A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26863 AN: 152052 Hom.: 3787 Cov.: 33

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.0867

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.0431

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.0741

Gnomad OTH AF: 0.153

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

GnomAD4 genome AF: 0.177 AC: 26916 AN: 152170 Hom.: 3793 Cov.: 33 AF XY: 0.175 AC XY: 13051 AN XY: 74404

Gnomad4 AFR AF: 0.389

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.0867

Gnomad4 EAS AF: 0.268

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.0431

Gnomad4 NFE AF: 0.0741

Gnomad4 OTH AF: 0.154

Alfa AF: 0.101 Hom.: 602

Bravo AF: 0.193

Asia WGS AF: 0.258 AC: 896 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	0.19
Dann	Benign	0.58

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1205918; hg19: chr6-22365762;