rs2078543

Variant names:

• chr6-21996631-A-G
• rs2078543
• ENST00000444265.6:n.317+17569A>G

Variant summary

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

The ENST00000444265.6(CASC15):​n.317+17569A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.699 in 152,090 control chromosomes in the GnomAD database, including 37,462 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 0.70 (37462 hom., cov: 32)
• Consequence: CASC15 ENST00000444265.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.978
• Publications: 9 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC15	NR_015410.2	n.899+17569A>G		intron_variant	Intron 6 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000444265.6	n.317+17569A>G		intron_variant	Intron 3 of 10	1
CASC15	ENST00000606851.5	n.868+17569A>G		intron_variant	Intron 6 of 11	2
CASC15	ENST00000607048.5	n.494+17569A>G		intron_variant	Intron 5 of 11	2

Frequencies

GnomAD3 genomes AF: 0.699 AC: 106194 AN: 151972 Hom.: 37457 Cov.: 32

Gnomad AFR AF: 0.659

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.745

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.981

Gnomad SAS AF: 0.808

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.709

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

GnomAD4 genome AF: 0.699 AC: 106245 AN: 152090 Hom.: 37462 Cov.: 32 AF XY: 0.701 AC XY: 52159 AN XY: 74368

African (AFR) AF: 0.659 AC: 27302 AN: 41452

American (AMR) AF: 0.745 AC: 11374 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.635 AC: 2205 AN: 3470

East Asian (EAS) AF: 0.981 AC: 5074 AN: 5174

South Asian (SAS) AF: 0.807 AC: 3894 AN: 4828

European-Finnish (FIN) AF: 0.653 AC: 6910 AN: 10580

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.693 AC: 47091 AN: 67998

Other (OTH) AF: 0.710 AC: 1495 AN: 2106

Alfa AF: 0.699 Hom.: 143977

Bravo AF: 0.703

Asia WGS AF: 0.860 AC: 2989 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.15
DANN	Benign	0.30
PhyloP100		-0.98

Splicing

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

Other links and lift over

dbSNP: rs2078543; hg19: chr6-21996860;