6-22285783-A-G

Variant names:

• chr6-22285783-A-G
• rs1205961
• ENST00000561912.3:n.459-5095A>G

Variant summary

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

The ENST00000561912.3(CASC15):​n.459-5095A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 151,704 control chromosomes in the GnomAD database, including 25,385 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 0.56 (25385 hom., cov: 31)
• Consequence: CASC15 ENST00000561912.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000561912.3	n.459-5095A>G		intron_variant	Intron 3 of 10	5
CASC15	ENST00000651569.1	n.376-5076A>G		intron_variant	Intron 3 of 7

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84355 AN: 151584 Hom.: 25377 Cov.: 31

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.687

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.952

Gnomad SAS AF: 0.686

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.637

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.600

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

GnomAD4 genome AF: 0.556 AC: 84403 AN: 151704 Hom.: 25385 Cov.: 31 AF XY: 0.565 AC XY: 41869 AN XY: 74102

Gnomad4 AFR AF: 0.318

Gnomad4 AMR AF: 0.660

Gnomad4 ASJ AF: 0.601

Gnomad4 EAS AF: 0.952

Gnomad4 SAS AF: 0.686

Gnomad4 FIN AF: 0.606

Gnomad4 NFE AF: 0.625

Gnomad4 OTH AF: 0.600

Alfa AF: 0.624 Hom.: 39328

Bravo AF: 0.552

Asia WGS AF: 0.771 AC: 2680 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.34
DANN	Benign	0.47

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1205961; hg19: chr6-22286012;