rs12207718

Variant names:

• chr6-22109338-T-G
• rs12207718
• ENST00000444265.6:n.888-1409T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000444265.6(CASC15):​n.888-1409T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0292 in 152,268 control chromosomes in the GnomAD database, including 90 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 0.029 (90 hom., cov: 32)
• Consequence: CASC15 ENST00000444265.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58
• Publications: 1 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0292 (4447/152268) while in subpopulation NFE AF = 0.0436 (2966/68026). AF 95% confidence interval is 0.0423. There are 90 homozygotes in GnomAd4. There are 2099 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 90 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC15	NR_015410.2	n.1249-1409T>G		intron_variant	Intron 8 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000444265.6	n.888-1409T>G		intron_variant	Intron 6 of 10	1
CASC15	ENST00000606851.5	n.1218-1409T>G		intron_variant	Intron 8 of 11	2
CASC15	ENST00000607048.5	n.844-1409T>G		intron_variant	Intron 7 of 11	2

Frequencies

GnomAD3 genomes AF: 0.0292 AC: 4447 AN: 152150 Hom.: 90 Cov.: 32

Gnomad AFR AF: 0.00782

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0350

Gnomad ASJ AF: 0.0458

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.00725

Gnomad FIN AF: 0.0316

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0436

Gnomad OTH AF: 0.0397

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

GnomAD4 genome AF: 0.0292 AC: 4447 AN: 152268 Hom.: 90 Cov.: 32 AF XY: 0.0282 AC XY: 2099 AN XY: 74462

African (AFR) AF: 0.00780 AC: 324 AN: 41550

American (AMR) AF: 0.0350 AC: 535 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0458 AC: 159 AN: 3470

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5186

South Asian (SAS) AF: 0.00705 AC: 34 AN: 4826

European-Finnish (FIN) AF: 0.0316 AC: 335 AN: 10602

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0436 AC: 2966 AN: 68026

Other (OTH) AF: 0.0393 AC: 83 AN: 2112

Alfa AF: 0.0397 Hom.: 214

Bravo AF: 0.0279

Asia WGS AF: 0.00520 AC: 19 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.040
DANN	Benign	0.63
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs12207718; hg19: chr6-22109567;