ENST00000561912.3:n.1348-1278G>A

Variant names:

• chr6-22366936-G-A
• rs10484723
• ENST00000561912.3:n.1348-1278G>A

Variant summary

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

The ENST00000561912.3(CASC15):​n.1348-1278G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 152,070 control chromosomes in the GnomAD database, including 8,692 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 0.31 (8692 hom., cov: 32)
• Consequence: CASC15 ENST00000561912.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.66
• Publications: 2 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]

LOC105374971 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105374971	XR_001744023.2	n.368-1278G>A		intron_variant	Intron 2 of 3
LOC105374971	XR_001744024.2	n.367+14285G>A		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000561912.3	n.1348-1278G>A		intron_variant	Intron 10 of 10	5
CASC15	ENST00000652081.2	n.145+14285G>A		intron_variant	Intron 2 of 7
CASC15	ENST00000846434.1	n.346+14285G>A		intron_variant	Intron 2 of 5

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46404 AN: 151952 Hom.: 8692 Cov.: 32

Gnomad AFR AF: 0.0796

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.305 AC: 46418 AN: 152070 Hom.: 8692 Cov.: 32 AF XY: 0.309 AC XY: 22931 AN XY: 74316

African (AFR) AF: 0.0793 AC: 3293 AN: 41512

American (AMR) AF: 0.322 AC: 4920 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1210 AN: 3468

East Asian (EAS) AF: 0.385 AC: 1983 AN: 5154

South Asian (SAS) AF: 0.267 AC: 1286 AN: 4818

European-Finnish (FIN) AF: 0.446 AC: 4709 AN: 10562

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.410 AC: 27851 AN: 67956

Other (OTH) AF: 0.313 AC: 662 AN: 2112

Alfa AF: 0.353 Hom.: 3171

Bravo AF: 0.288

Asia WGS AF: 0.283 AC: 985 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	18
DANN	Benign	0.58
PhyloP100		2.7

Splicing

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

Other links and lift over

dbSNP: rs10484723; hg19: chr6-22367165;