6-22060353-T-C

Variant names:

• chr6-22060353-T-C
• rs885769
• ENST00000444265.6:n.667-2667T>C

Variant summary

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

The ENST00000444265.6(CASC15):​n.667-2667T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.71 in 152,076 control chromosomes in the GnomAD database, including 38,999 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 0.71 (38999 hom., cov: 32)
• Consequence: CASC15 ENST00000444265.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0820
• Publications: 3 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC15	NR_015410.2	n.1248+3663T>C		intron_variant	Intron 8 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000444265.6	n.667-2667T>C		intron_variant	Intron 5 of 10	1
CASC15	ENST00000606851.5	n.1217+3663T>C		intron_variant	Intron 8 of 11	2
CASC15	ENST00000607048.5	n.843+3663T>C		intron_variant	Intron 7 of 11	2

Frequencies

GnomAD3 genomes AF: 0.710 AC: 107853 AN: 151958 Hom.: 38965 Cov.: 32

Gnomad AFR AF: 0.818

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.711

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.904

Gnomad SAS AF: 0.746

Gnomad FIN AF: 0.740

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.631

Gnomad OTH AF: 0.665

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

GnomAD4 genome AF: 0.710 AC: 107938 AN: 152076 Hom.: 38999 Cov.: 32 AF XY: 0.716 AC XY: 53163 AN XY: 74298

African (AFR) AF: 0.818 AC: 33930 AN: 41482

American (AMR) AF: 0.712 AC: 10875 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.557 AC: 1932 AN: 3470

East Asian (EAS) AF: 0.904 AC: 4677 AN: 5172

South Asian (SAS) AF: 0.744 AC: 3587 AN: 4822

European-Finnish (FIN) AF: 0.740 AC: 7803 AN: 10550

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.631 AC: 42887 AN: 67982

Other (OTH) AF: 0.659 AC: 1394 AN: 2114

Alfa AF: 0.651 Hom.: 18090

Bravo AF: 0.714

Asia WGS AF: 0.728 AC: 2535 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.36
PhyloP100		-0.082

Splicing

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

Other links and lift over

dbSNP: rs885769; hg19: chr6-22060582;