ENST00000561912.3:n.1348-2681A>G

Variant names:

• chr6-22365533-A-G
• rs1205918
• ENST00000561912.3:n.1348-2681A>G

Variant summary

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

Score: -12 - Benign

-12

BP4_StrongBA1

The ENST00000561912.3(CASC15):​n.1348-2681A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,170 control chromosomes in the GnomAD database, including 3,793 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 0.18 (3793 hom., cov: 33)
• Consequence: CASC15 ENST00000561912.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105374971	XR_001744023.2	n.368-2681A>G		intron_variant	Intron 2 of 3
LOC105374971	XR_001744024.2	n.367+12882A>G		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000561912.3	n.1348-2681A>G		intron_variant	Intron 10 of 10	5
CASC15	ENST00000652081.2	n.145+12882A>G		intron_variant	Intron 2 of 7
CASC15	ENST00000846434.1	n.346+12882A>G		intron_variant	Intron 2 of 5

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26863 AN: 152052 Hom.: 3787 Cov.: 33

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.0867

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.0431

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.0741

Gnomad OTH AF: 0.153

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

GnomAD4 genome AF: 0.177 AC: 26916 AN: 152170 Hom.: 3793 Cov.: 33 AF XY: 0.175 AC XY: 13051 AN XY: 74404

African (AFR) AF: 0.389 AC: 16120 AN: 41482

American (AMR) AF: 0.153 AC: 2332 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0867 AC: 301 AN: 3470

East Asian (EAS) AF: 0.268 AC: 1385 AN: 5162

South Asian (SAS) AF: 0.170 AC: 820 AN: 4828

European-Finnish (FIN) AF: 0.0431 AC: 457 AN: 10608

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.0741 AC: 5039 AN: 68016

Other (OTH) AF: 0.154 AC: 326 AN: 2114

Alfa AF: 0.111 Hom.: 1322

Bravo AF: 0.193

Asia WGS AF: 0.258 AC: 896 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.19
DANN	Benign	0.58
PhyloP100		-1.5

Splicing

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

Other links and lift over

dbSNP: rs1205918; hg19: chr6-22365762;