6-22125735-T-C

Variant names:

• chr6-22125735-T-C
• rs4712653
• ENST00000444265.6:n.1061+14815T>C

Variant summary

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

The ENST00000444265.6(CASC15):​n.1061+14815T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 152,084 control chromosomes in the GnomAD database, including 29,226 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 0.60 (29226 hom., cov: 32)
• Consequence: CASC15 ENST00000444265.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.478
• Publications: 38 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=-0.62).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC15	NR_015410.2	n.1422+14815T>C		intron_variant	Intron 9 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000444265.6	n.1061+14815T>C		intron_variant	Intron 7 of 10	1
CASC15	ENST00000606851.5	n.1391+14815T>C		intron_variant	Intron 9 of 11	2
CASC15	ENST00000607048.5	n.1138+11698T>C		intron_variant	Intron 9 of 11	2

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91114 AN: 151964 Hom.: 29187 Cov.: 32

Gnomad AFR AF: 0.819

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.738

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.556

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

GnomAD4 genome AF: 0.600 AC: 91209 AN: 152084 Hom.: 29226 Cov.: 32 AF XY: 0.605 AC XY: 44952 AN XY: 74354

African (AFR) AF: 0.819 AC: 34012 AN: 41512

American (AMR) AF: 0.624 AC: 9532 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 1500 AN: 3464

East Asian (EAS) AF: 0.738 AC: 3809 AN: 5162

South Asian (SAS) AF: 0.634 AC: 3059 AN: 4822

European-Finnish (FIN) AF: 0.574 AC: 6063 AN: 10562

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.462 AC: 31396 AN: 67962

Other (OTH) AF: 0.551 AC: 1163 AN: 2112

Alfa AF: 0.498 Hom.: 86516

Bravo AF: 0.613

Asia WGS AF: 0.672 AC: 2334 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	12
DANN	Benign	0.87
PhyloP100		0.48

Splicing

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

Other links and lift over

dbSNP: rs4712653; hg19: chr6-22125964;