rs12207718

chr6-22109338-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NR_015410.2(CASC15):n.1249-1409T>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 0.0292 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 NR_015410.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58

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

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 90 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASC15	NR_015410.2	n.1249-1409T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASC15	ENST00000688254.1	n.1151+52648T>G		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.00780

Gnomad4 AMR AF: 0.0350

Gnomad4 ASJ AF: 0.0458

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.00705

Gnomad4 FIN AF: 0.0316

Gnomad4 NFE AF: 0.0436

Gnomad4 OTH AF: 0.0393

Alfa AF: 0.0409 Hom.: 180

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12207718; hg19: chr6-22109567;