rs3749995

Positions:

• chr6-22117206-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.1422+6286C>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 0.0392 in 152,172 control chromosomes in the GnomAD database, including 205 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 0.039 (205 hom., cov: 32)
• Consequence: CASC15 NR_015410.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.390

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASC15	NR_015410.2	n.1422+6286C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASC15	ENST00000688254.1	n.1151+60516C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0392 AC: 5960 AN: 152054 Hom.: 204 Cov.: 32

Gnomad AFR AF: 0.0567

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0260

Gnomad ASJ AF: 0.00865

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.0213

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0237

Gnomad OTH AF: 0.0268

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

GnomAD4 genome AF: 0.0392 AC: 5965 AN: 152172 Hom.: 205 Cov.: 32 AF XY: 0.0406 AC XY: 3020 AN XY: 74356

Gnomad4 AFR AF: 0.0567

Gnomad4 AMR AF: 0.0259

Gnomad4 ASJ AF: 0.00865

Gnomad4 EAS AF: 0.101

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.0213

Gnomad4 NFE AF: 0.0237

Gnomad4 OTH AF: 0.0260

Alfa AF: 0.0251 Hom.: 56

Bravo AF: 0.0369

Asia WGS AF: 0.104 AC: 361 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.23
DANN	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3749995; hg19: chr6-22117435;