rs1928168

Variant names:

• chr6-22017509-T-C
• rs1928168
• ENST00000444265.6:n.318-2830T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000444265.6(CASC15):​n.318-2830T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 151,720 control chromosomes in the GnomAD database, including 11,651 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 (11651 hom., cov: 30)
• Consequence: CASC15 ENST00000444265.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.104

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC15	NR_015410.2	n.900-2830T>C		intron_variant	Intron 6 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000444265.6	n.318-2830T>C		intron_variant	Intron 3 of 10	1
CASC15	ENST00000606851.5	n.869-2830T>C		intron_variant	Intron 6 of 11	2
CASC15	ENST00000607048.5	n.495-2830T>C		intron_variant	Intron 5 of 11	2

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54839 AN: 151602 Hom.: 11651 Cov.: 30

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.361 AC: 54838 AN: 151720 Hom.: 11651 Cov.: 30 AF XY: 0.360 AC XY: 26712 AN XY: 74134

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.334

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.186

Gnomad4 SAS AF: 0.499

Gnomad4 FIN AF: 0.466

Gnomad4 NFE AF: 0.490

Gnomad4 OTH AF: 0.355

Alfa AF: 0.451 Hom.: 20457

Bravo AF: 0.336

Asia WGS AF: 0.363 AC: 1263 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1928168; hg19: chr6-22017738;