rs2000191

Positions:

• chr6-22504519-A-C
• chr6-22504519-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.483-13166A>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 0.0523 in 152,266 control chromosomes in the GnomAD database, including 261 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 0.052 (261 hom., cov: 32)
• Consequence: LOC105374971 XR_001744024.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0150

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105374971	XR_001744024.2	n.483-13166A>C		intron_variant, non_coding_transcript_variant
LOC105374971	XR_001744025.1	n.403-13166A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000652081.1	n.146-69600A>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0523 AC: 7958 AN: 152148 Hom.: 261 Cov.: 32

Gnomad AFR AF: 0.0224

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.0613

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.0208

Gnomad SAS AF: 0.0734

Gnomad FIN AF: 0.0588

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0647

Gnomad OTH AF: 0.0554

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

GnomAD4 genome AF: 0.0523 AC: 7961 AN: 152266 Hom.: 261 Cov.: 32 AF XY: 0.0521 AC XY: 3879 AN XY: 74448

Gnomad4 AFR AF: 0.0225

Gnomad4 AMR AF: 0.0613

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.0210

Gnomad4 SAS AF: 0.0730

Gnomad4 FIN AF: 0.0588

Gnomad4 NFE AF: 0.0647

Gnomad4 OTH AF: 0.0548

Alfa AF: 0.0621 Hom.: 419

Bravo AF: 0.0515

Asia WGS AF: 0.0590 AC: 206 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.47

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2000191; hg19: chr6-22504748;