chr6-21817734-G-C

Variant names:

• chr6-21817734-G-C
• rs6918975
• ENST00000606336.5:n.920+34026G>C

Variant summary

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

The ENST00000606336.5(CASC15):​n.920+34026G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.752 in 152,160 control chromosomes in the GnomAD database, including 43,534 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 0.75 (43534 hom., cov: 33)
• Consequence: CASC15 ENST00000606336.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.943
• Publications: 0 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 (EAS) allele frequency at 95% confidence interval = 0.863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC15	NR_015410.2	n.647+14994G>C		intron_variant	Intron 4 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000606336.5	n.920+34026G>C		intron_variant	Intron 6 of 6	1
CASC15	ENST00000606851.5	n.616+14994G>C		intron_variant	Intron 4 of 11	2
CASC15	ENST00000607048.5	n.242+14994G>C		intron_variant	Intron 3 of 11	2

Frequencies

GnomAD3 genomes AF: 0.752 AC: 114364 AN: 152042 Hom.: 43479 Cov.: 33

Gnomad AFR AF: 0.859

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.802

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.884

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.769

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

GnomAD4 genome AF: 0.752 AC: 114467 AN: 152160 Hom.: 43534 Cov.: 33 AF XY: 0.750 AC XY: 55796 AN XY: 74378

African (AFR) AF: 0.859 AC: 35696 AN: 41552

American (AMR) AF: 0.802 AC: 12247 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.671 AC: 2328 AN: 3472

East Asian (EAS) AF: 0.884 AC: 4576 AN: 5174

South Asian (SAS) AF: 0.592 AC: 2853 AN: 4818

European-Finnish (FIN) AF: 0.671 AC: 7089 AN: 10568

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.695 AC: 47253 AN: 67990

Other (OTH) AF: 0.761 AC: 1605 AN: 2108

Alfa AF: 0.713 Hom.: 4847

Bravo AF: 0.776

Asia WGS AF: 0.688 AC: 2394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	13
DANN	Benign	0.45
PhyloP100		0.94

Splicing

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

Other links and lift over

dbSNP: rs6918975; hg19: chr6-21817965;