rs6917811

chr6-21800414-C-T

Variant summary

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

The NR_015410.2(CASC15):n.564-2243C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,022 control chromosomes in the GnomAD database, including 3,665 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 0.20 (3665 hom., cov: 32)
• Consequence: CASC15 NR_015410.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.473

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 (AFR) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASC15	NR_015410.2	n.564-2243C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASC15	ENST00000688254.1	n.550+16706C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30691 AN: 151904 Hom.: 3659 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.0634

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.178

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

GnomAD4 genome AF: 0.202 AC: 30719 AN: 152022 Hom.: 3665 Cov.: 32 AF XY: 0.194 AC XY: 14444 AN XY: 74310

Gnomad4 AFR AF: 0.314

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0635

Gnomad4 FIN AF: 0.149

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.176

Alfa AF: 0.198 Hom.: 458

Bravo AF: 0.209

Asia WGS AF: 0.0460 AC: 161 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	3.2
Dann	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6917811; hg19: chr6-21800645;