6-22055902-A-G

Variant names:

• chr6-22055902-A-G
• rs196051
• ENST00000444265.6:n.522-644A>G

Variant summary

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

The ENST00000444265.6(CASC15):​n.522-644A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 151,992 control chromosomes in the GnomAD database, including 22,166 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 0.52 (22166 hom., cov: 32)
• Consequence: CASC15 ENST00000444265.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.316
• Publications: 4 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 = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC15	NR_015410.2	n.1104-644A>G		intron_variant	Intron 7 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000444265.6	n.522-644A>G		intron_variant	Intron 4 of 10	1
CASC15	ENST00000606851.5	n.1073-644A>G		intron_variant	Intron 7 of 11	2
CASC15	ENST00000607048.5	n.699-644A>G		intron_variant	Intron 6 of 11	2

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78841 AN: 151876 Hom.: 22122 Cov.: 32

Gnomad AFR AF: 0.692

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.853

Gnomad SAS AF: 0.569

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.524

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

GnomAD4 genome AF: 0.519 AC: 78931 AN: 151992 Hom.: 22166 Cov.: 32 AF XY: 0.524 AC XY: 38892 AN XY: 74292

African (AFR) AF: 0.692 AC: 28672 AN: 41428

American (AMR) AF: 0.577 AC: 8815 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1742 AN: 3464

East Asian (EAS) AF: 0.853 AC: 4406 AN: 5166

South Asian (SAS) AF: 0.569 AC: 2748 AN: 4828

European-Finnish (FIN) AF: 0.382 AC: 4032 AN: 10562

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.397 AC: 26985 AN: 67958

Other (OTH) AF: 0.529 AC: 1118 AN: 2112

Alfa AF: 0.459 Hom.: 13632

Bravo AF: 0.544

Asia WGS AF: 0.718 AC: 2492 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.67
DANN	Benign	0.66
PhyloP100		-0.32

Splicing

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

Other links and lift over

dbSNP: rs196051; hg19: chr6-22056131;