rs12207699

chr6-21929655-A-Gchr6-21929655-A-T

Variant summary

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

The NR_015410.2(CASC15):n.781+20052A>G 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 0.364 in 151,980 control chromosomes in the GnomAD database, including 10,495 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 (10495 hom., cov: 32)
• Consequence: CASC15 NR_015410.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.421

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=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASC15	NR_015410.2	n.781+20052A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASC15	ENST00000688254.1	n.684+20052A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55217 AN: 151864 Hom.: 10487 Cov.: 32

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.369

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

GnomAD4 genome AF: 0.364 AC: 55255 AN: 151980 Hom.: 10495 Cov.: 32 AF XY: 0.358 AC XY: 26597 AN XY: 74270

Gnomad4 AFR AF: 0.310

Gnomad4 AMR AF: 0.315

Gnomad4 ASJ AF: 0.443

Gnomad4 EAS AF: 0.132

Gnomad4 SAS AF: 0.318

Gnomad4 FIN AF: 0.397

Gnomad4 NFE AF: 0.418

Gnomad4 OTH AF: 0.366

Alfa AF: 0.407 Hom.: 19092

Bravo AF: 0.356

Asia WGS AF: 0.212 AC: 739 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.36
Dann	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12207699; hg19: chr6-21929886;