6-22224149-T-G

Position:

• chr6-22224149-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000561912.3(CASC15):​n.200-32225T>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 0.0552 in 152,288 control chromosomes in the GnomAD database, including 238 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 0.055 (238 hom., cov: 33)
• Consequence: CASC15 ENST00000561912.3 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.768

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000561912.3	n.200-32225T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0552 AC: 8397 AN: 152170 Hom.: 238 Cov.: 33

Gnomad AFR AF: 0.0533

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.0368

Gnomad ASJ AF: 0.0216

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.0385

Gnomad FIN AF: 0.0857

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0612

Gnomad OTH AF: 0.0589

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

GnomAD4 genome AF: 0.0552 AC: 8403 AN: 152288 Hom.: 238 Cov.: 33 AF XY: 0.0553 AC XY: 4121 AN XY: 74464

Gnomad4 AFR AF: 0.0532

Gnomad4 AMR AF: 0.0367

Gnomad4 ASJ AF: 0.0216

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.0387

Gnomad4 FIN AF: 0.0857

Gnomad4 NFE AF: 0.0612

Gnomad4 OTH AF: 0.0587

Alfa AF: 0.0568 Hom.: 330

Bravo AF: 0.0513

Asia WGS AF: 0.0220 AC: 75 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	15
DANN	Benign	0.83

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6937402; hg19: chr6-22224378;