ENST00000444265.6:n.887+6607G>A

Variant names:

• chr6-22069847-G-A
• rs9295533
• ENST00000444265.6:n.887+6607G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000444265.6(CASC15):​n.887+6607G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0829 in 152,002 control chromosomes in the GnomAD database, including 1,036 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 0.083 (1036 hom., cov: 32)
• Consequence: CASC15 ENST00000444265.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32
• Publications: 0 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=-0.67).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000444265.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC15	NR_015410.2		n.1248+13157G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC15	ENST00000444265.6	TSL:1	n.887+6607G>A		intron	N/A
	CASC15	ENST00000606851.5	TSL:2	n.1217+13157G>A		intron	N/A
	CASC15	ENST00000607048.5	TSL:2	n.843+13157G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0828 AC: 12580 AN: 151884 Hom.: 1031 Cov.: 32

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0288

Gnomad EAS AF: 0.0566

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.0177

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0165

Gnomad OTH AF: 0.0703

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

GnomAD4 genome AF: 0.0829 AC: 12597 AN: 152002 Hom.: 1036 Cov.: 32 AF XY: 0.0835 AC XY: 6201 AN XY: 74306

African (AFR) AF: 0.200 AC: 8301 AN: 41424

American (AMR) AF: 0.102 AC: 1560 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0288 AC: 100 AN: 3470

East Asian (EAS) AF: 0.0565 AC: 292 AN: 5164

South Asian (SAS) AF: 0.179 AC: 860 AN: 4814

European-Finnish (FIN) AF: 0.0177 AC: 187 AN: 10560

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0165 AC: 1123 AN: 67980

Other (OTH) AF: 0.0695 AC: 147 AN: 2114

Alfa AF: 0.0351 Hom.: 799

Bravo AF: 0.0909

Asia WGS AF: 0.115 AC: 397 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	8.7
DANN	Benign	0.82
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs9295533; hg19: chr6-22070076;