6-22005223-T-C

Variant names:

• chr6-22005223-T-C
• rs10946498
• ENST00000444265.6:n.318-15116T>C

Variant summary

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

The ENST00000444265.6(CASC15):​n.318-15116T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,174 control chromosomes in the GnomAD database, including 1,520 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 0.10 (1520 hom., cov: 31)
• Consequence: CASC15 ENST00000444265.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77
• 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=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC15	NR_015410.2	n.900-15116T>C		intron_variant	Intron 6 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000444265.6	n.318-15116T>C		intron_variant	Intron 3 of 10	1
CASC15	ENST00000606851.5	n.869-15116T>C		intron_variant	Intron 6 of 11	2
CASC15	ENST00000607048.5	n.495-15116T>C		intron_variant	Intron 5 of 11	2

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15370 AN: 152056 Hom.: 1516 Cov.: 31

Gnomad AFR AF: 0.0243

Gnomad AMI AF: 0.0903

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.0931

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0882

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.101 AC: 15379 AN: 152174 Hom.: 1520 Cov.: 31 AF XY: 0.108 AC XY: 8000 AN XY: 74410

African (AFR) AF: 0.0242 AC: 1005 AN: 41532

American (AMR) AF: 0.219 AC: 3349 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 410 AN: 3470

East Asian (EAS) AF: 0.468 AC: 2413 AN: 5160

South Asian (SAS) AF: 0.185 AC: 892 AN: 4822

European-Finnish (FIN) AF: 0.0931 AC: 988 AN: 10608

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0882 AC: 5996 AN: 67978

Other (OTH) AF: 0.106 AC: 224 AN: 2114

Alfa AF: 0.0966 Hom.: 128

Bravo AF: 0.111

Asia WGS AF: 0.295 AC: 1026 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.61
DANN	Benign	0.47
PhyloP100		-1.8

Splicing

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

Other links and lift over

dbSNP: rs10946498; hg19: chr6-22005452;