rs12523974

Variant names:

• chr6-22073692-G-A
• rs12523974
• ENST00000444265.6:n.887+10452G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-22073692-G-A
• chr6-22073692-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000444265.6(CASC15):​n.887+10452G>A variant causes a intron 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 ENST00000444265.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CASC15	NR_015410.2	n.1248+17002G>A		intron_variant	Intron 8 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000444265.6	n.887+10452G>A		intron_variant	Intron 6 of 10	1
CASC15	ENST00000606851.5	n.1217+17002G>A		intron_variant	Intron 8 of 11	2
CASC15	ENST00000607048.5	n.843+17002G>A		intron_variant	Intron 7 of 11	2

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

African (AFR) AF: 0.174 AC: 7199 AN: 41482

American (AMR) AF: 0.212 AC: 3241 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0314 AC: 109 AN: 3470

East Asian (EAS) AF: 0.649 AC: 3350 AN: 5160

South Asian (SAS) AF: 0.156 AC: 753 AN: 4814

European-Finnish (FIN) AF: 0.0741 AC: 785 AN: 10590

Middle Eastern (MID) AF: 0.0342 AC: 10 AN: 292

European-Non Finnish (NFE) AF: 0.0102 AC: 692 AN: 68006

Other (OTH) AF: 0.0922 AC: 195 AN: 2114

Alfa AF: 0.0239 Hom.: 29

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
PhyloP100		-1.5

Splicing

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

Other links and lift over

dbSNP: rs12523974; hg19: chr6-22073921;