6-21699111-A-G

Position:

• chr6-21699111-A-G

Variant summary

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

The ENST00000606336.5(CASC15):​n.575+30212A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.904 in 152,190 control chromosomes in the GnomAD database, including 62,395 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 0.90 (62395 hom., cov: 31)
• Consequence: CASC15 ENST00000606336.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0420

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASC15	NR_015410.2	n.486+30212A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000606336.5	n.575+30212A>G		intron_variant		1
CASC15	ENST00000606851.5	n.455+30212A>G		intron_variant		2
CASC15	ENST00000607048.5	n.81+30212A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.904 AC: 137469 AN: 152072 Hom.: 62332 Cov.: 31

Gnomad AFR AF: 0.977

Gnomad AMI AF: 0.870

Gnomad AMR AF: 0.909

Gnomad ASJ AF: 0.839

Gnomad EAS AF: 0.978

Gnomad SAS AF: 0.781

Gnomad FIN AF: 0.869

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.872

Gnomad OTH AF: 0.878

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

GnomAD4 genome AF: 0.904 AC: 137589 AN: 152190 Hom.: 62395 Cov.: 31 AF XY: 0.902 AC XY: 67088 AN XY: 74402

Gnomad4 AFR AF: 0.977

Gnomad4 AMR AF: 0.909

Gnomad4 ASJ AF: 0.839

Gnomad4 EAS AF: 0.978

Gnomad4 SAS AF: 0.780

Gnomad4 FIN AF: 0.869

Gnomad4 NFE AF: 0.872

Gnomad4 OTH AF: 0.880

Alfa AF: 0.891 Hom.: 14582

Bravo AF: 0.915

Asia WGS AF: 0.860 AC: 2990 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.0
DANN	Benign	0.48

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4712625; hg19: chr6-21699342;