rs13198653

chr6-22209381-T-Cchr6-22209381-T-G

Variant summary

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

The ENST00000444265.6(CASC15):n.1298+4122T>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 0.122 in 152,222 control chromosomes in the GnomAD database, including 1,501 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 0.12 (1501 hom., cov: 32)
• Consequence: CASC15 ENST00000444265.6 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30

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).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASC15	ENST00000688254.1	n.1152-4926T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18516 AN: 152104 Hom.: 1501 Cov.: 32

Gnomad AFR AF: 0.0365

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.0900

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.00520

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.122 AC: 18511 AN: 152222 Hom.: 1501 Cov.: 32 AF XY: 0.120 AC XY: 8949 AN XY: 74434

Gnomad4 AFR AF: 0.0366

Gnomad4 AMR AF: 0.0899

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.00521

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.131

Alfa AF: 0.170 Hom.: 2555

Bravo AF: 0.112

Asia WGS AF: 0.0920 AC: 320 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	5.3
Dann	Benign	0.54

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13198653; hg19: chr6-22209610;