6-22312733-A-G

Variant names:

• chr6-22312733-A-G
• rs12525289
• ENST00000561912.3:n.570-4094A>G

Variant summary

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

The ENST00000561912.3(CASC15):​n.570-4094A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,122 control chromosomes in the GnomAD database, including 8,924 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 0.31 (8924 hom., cov: 32)
• Consequence: CASC15 ENST00000561912.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.329
• Publications: 2 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000561912.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC15	ENST00000561912.3	TSL:5	n.570-4094A>G		intron	N/A
	CASC15	ENST00000651569.1		n.506-4094A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.309 AC: 47021 AN: 152004 Hom.: 8924 Cov.: 32

Gnomad AFR AF: 0.0829

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.309 AC: 47038 AN: 152122 Hom.: 8924 Cov.: 32 AF XY: 0.312 AC XY: 23217 AN XY: 74346

African (AFR) AF: 0.0827 AC: 3436 AN: 41534

American (AMR) AF: 0.331 AC: 5064 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1327 AN: 3470

East Asian (EAS) AF: 0.389 AC: 2005 AN: 5156

South Asian (SAS) AF: 0.266 AC: 1282 AN: 4816

European-Finnish (FIN) AF: 0.441 AC: 4658 AN: 10564

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.414 AC: 28114 AN: 67988

Other (OTH) AF: 0.332 AC: 701 AN: 2112

Alfa AF: 0.344 Hom.: 1332

Bravo AF: 0.292

Asia WGS AF: 0.287 AC: 999 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.5
DANN	Benign	0.66
PhyloP100		0.33

Splicing

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

Other links and lift over

dbSNP: rs12525289; hg19: chr6-22312962;