rs10485008

chr6-22506402-G-A

Variant summary

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

The XR_001744024.2(LOC105374971):n.483-11283G>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 0.138 in 152,188 control chromosomes in the GnomAD database, including 1,811 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 0.14 (1811 hom., cov: 33)
• Consequence: LOC105374971 XR_001744024.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.172

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC105374971	XR_001744024.2	n.483-11283G>A		intron_variant, non_coding_transcript_variant
LOC105374971	XR_001744025.1	n.403-11283G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASC15	ENST00000652081.1	n.146-67717G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20943 AN: 152070 Hom.: 1812 Cov.: 33

Gnomad AFR AF: 0.0548

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.00925

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.138 AC: 20942 AN: 152188 Hom.: 1811 Cov.: 33 AF XY: 0.133 AC XY: 9926 AN XY: 74402

Gnomad4 AFR AF: 0.0547

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.00927

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.179

Alfa AF: 0.154 Hom.: 385

Bravo AF: 0.136

Asia WGS AF: 0.0770 AC: 269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	2.2
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: rs10485008; hg19: chr6-22506631;