rs12523974

chr6-22073692-G-Achr6-22073692-G-C

Variant summary

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

The NR_015410.2(CASC15):n.1248+17002G>A 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 0.107 in 152,098 control chromosomes in the GnomAD database, including 2,326 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 0.11 (2326 hom., cov: 32)
• Consequence: CASC15 NR_015410.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASC15	NR_015410.2	n.1248+17002G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASC15	ENST00000688254.1	n.1151+17002G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16315 AN: 151980 Hom.: 2326 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.0314

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.0741

Gnomad MID AF: 0.0350

Gnomad NFE AF: 0.0102

Gnomad OTH AF: 0.0923

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

GnomAD4 genome AF: 0.107 AC: 16343 AN: 152098 Hom.: 2326 Cov.: 32 AF XY: 0.117 AC XY: 8691 AN XY: 74354

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.0314

Gnomad4 EAS AF: 0.649

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.0741

Gnomad4 NFE AF: 0.0102

Gnomad4 OTH AF: 0.0922

Alfa AF: 0.0167 Hom.: 10

Bravo AF: 0.126

Asia WGS AF: 0.305 AC: 1058 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.0090
Dann	Benign	0.53

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12523974; hg19: chr6-22073921;