rs10485008

Variant names:

• chr6-22506402-G-A
• rs10485008
• ENST00000652081.2:n.146-67717G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000652081.2(CASC15):​n.146-67717G>A variant causes a intron 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: CASC15 ENST00000652081.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.172
• Publications: 2 publications found

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]

LOC105374971 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LOC105374971	XR_001744024.2	n.483-11283G>A		intron_variant	Intron 3 of 4
LOC105374971	XR_001744025.1	n.403-11283G>A		intron_variant	Intron 4 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000652081.2	n.146-67717G>A		intron_variant	Intron 2 of 7
CASC15	ENST00000846434.1	n.347-11283G>A		intron_variant	Intron 2 of 5
CASC15	ENST00000846435.1	n.352-11283G>A		intron_variant	Intron 2 of 2

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

African (AFR) AF: 0.0547 AC: 2271 AN: 41546

American (AMR) AF: 0.155 AC: 2373 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 722 AN: 3472

East Asian (EAS) AF: 0.00927 AC: 48 AN: 5178

South Asian (SAS) AF: 0.134 AC: 647 AN: 4818

European-Finnish (FIN) AF: 0.109 AC: 1149 AN: 10582

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.193 AC: 13093 AN: 67984

Other (OTH) AF: 0.179 AC: 379 AN: 2112

Alfa AF: 0.151 Hom.: 386

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
PhyloP100		-0.17

Splicing

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

Other links and lift over

dbSNP: rs10485008; hg19: chr6-22506631;