ENST00000444265.6:n.521+12239A>G

Variant names:

• chr6-22032781-A-G
• rs9350410
• ENST00000444265.6:n.521+12239A>G

Variant summary

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

The ENST00000444265.6(CASC15):​n.521+12239A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 150,864 control chromosomes in the GnomAD database, including 9,920 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 0.36 (9920 hom., cov: 29)
• Consequence: CASC15 ENST00000444265.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.693
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC15	NR_015410.2	n.1103+12239A>G		intron_variant	Intron 7 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000444265.6	n.521+12239A>G		intron_variant	Intron 4 of 10	1
CASC15	ENST00000606851.5	n.1072+12239A>G		intron_variant	Intron 7 of 11	2
CASC15	ENST00000607048.5	n.698+12239A>G		intron_variant	Intron 6 of 11	2

Frequencies

GnomAD3 genomes AF: 0.358 AC: 53941 AN: 150780 Hom.: 9914 Cov.: 29

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.0478

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.461

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.358 AC: 53967 AN: 150864 Hom.: 9920 Cov.: 29 AF XY: 0.353 AC XY: 26005 AN XY: 73590

African (AFR) AF: 0.408 AC: 16714 AN: 40980

American (AMR) AF: 0.321 AC: 4873 AN: 15174

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 1653 AN: 3470

East Asian (EAS) AF: 0.0478 AC: 245 AN: 5130

South Asian (SAS) AF: 0.196 AC: 932 AN: 4752

European-Finnish (FIN) AF: 0.380 AC: 3894 AN: 10258

Middle Eastern (MID) AF: 0.469 AC: 135 AN: 288

European-Non Finnish (NFE) AF: 0.360 AC: 24434 AN: 67830

Other (OTH) AF: 0.370 AC: 767 AN: 2072

Alfa AF: 0.359 Hom.: 22215

Bravo AF: 0.356

Asia WGS AF: 0.139 AC: 483 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.40
DANN	Benign	0.76
PhyloP100		-0.69

Splicing

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

Other links and lift over

dbSNP: rs9350410; hg19: chr6-22033010;