ENST00000444265.6:n.318-16673A>C

Variant names:

• chr6-22003666-A-C
• rs11966463
• ENST00000444265.6:n.318-16673A>C

Variant summary

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

The ENST00000444265.6(CASC15):​n.318-16673A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,172 control chromosomes in the GnomAD database, including 7,339 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 0.22 (7339 hom., cov: 32)
• Consequence: CASC15 ENST00000444265.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.619
• Publications: 8 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC15	NR_015410.2	n.900-16673A>C		intron_variant	Intron 6 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000444265.6	n.318-16673A>C		intron_variant	Intron 3 of 10	1
CASC15	ENST00000606851.5	n.869-16673A>C		intron_variant	Intron 6 of 11	2
CASC15	ENST00000607048.5	n.495-16673A>C		intron_variant	Intron 5 of 11	2

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32646 AN: 152054 Hom.: 7294 Cov.: 32

Gnomad AFR AF: 0.567

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0449

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.0536

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.215 AC: 32741 AN: 152172 Hom.: 7339 Cov.: 32 AF XY: 0.214 AC XY: 15899 AN XY: 74422

African (AFR) AF: 0.568 AC: 23553 AN: 41480

American (AMR) AF: 0.140 AC: 2134 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 360 AN: 3470

East Asian (EAS) AF: 0.303 AC: 1573 AN: 5184

South Asian (SAS) AF: 0.101 AC: 488 AN: 4818

European-Finnish (FIN) AF: 0.0449 AC: 477 AN: 10626

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.0536 AC: 3644 AN: 67998

Other (OTH) AF: 0.193 AC: 408 AN: 2110

Alfa AF: 0.108 Hom.: 5804

Bravo AF: 0.241

Asia WGS AF: 0.206 AC: 716 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.0
DANN	Benign	0.58
PhyloP100		0.62

Splicing

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

Other links and lift over

dbSNP: rs11966463; hg19: chr6-22003895;