rs11759745

Variant names:

• chr6-22114901-A-C
• rs11759745
• ENST00000444265.6:n.1061+3981A>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000444265.6(CASC15):​n.1061+3981A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 152,006 control chromosomes in the GnomAD database, including 10,596 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 0.37 (10596 hom., cov: 32)
• Consequence: CASC15 ENST00000444265.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100
• 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]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC15	NR_015410.2	n.1422+3981A>C		intron_variant	Intron 9 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000444265.6	n.1061+3981A>C		intron_variant	Intron 7 of 10	1
CASC15	ENST00000606851.5	n.1391+3981A>C		intron_variant	Intron 9 of 11	2
CASC15	ENST00000607048.5	n.1138+864A>C		intron_variant	Intron 9 of 11	2

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55547 AN: 151888 Hom.: 10587 Cov.: 32

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.348

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

GnomAD4 genome AF: 0.366 AC: 55588 AN: 152006 Hom.: 10596 Cov.: 32 AF XY: 0.365 AC XY: 27111 AN XY: 74298

African (AFR) AF: 0.453 AC: 18768 AN: 41428

American (AMR) AF: 0.314 AC: 4804 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 908 AN: 3464

East Asian (EAS) AF: 0.123 AC: 639 AN: 5178

South Asian (SAS) AF: 0.225 AC: 1086 AN: 4820

European-Finnish (FIN) AF: 0.440 AC: 4640 AN: 10550

Middle Eastern (MID) AF: 0.339 AC: 99 AN: 292

European-Non Finnish (NFE) AF: 0.344 AC: 23397 AN: 67966

Other (OTH) AF: 0.346 AC: 729 AN: 2106

Alfa AF: 0.339 Hom.: 12385

Bravo AF: 0.361

Asia WGS AF: 0.225 AC: 782 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	14
DANN	Benign	0.66
PhyloP100		0.0010

Splicing

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

Other links and lift over

dbSNP: rs11759745; hg19: chr6-22115130;