6-22117206-C-T

Variant names:

• chr6-22117206-C-T
• rs3749995
• ENST00000444265.6:n.1061+6286C>T

Variant summary

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

The ENST00000444265.6(CASC15):​n.1061+6286C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0392 in 152,172 control chromosomes in the GnomAD database, including 205 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 0.039 (205 hom., cov: 32)
• Consequence: CASC15 ENST00000444265.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.390
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC15	NR_015410.2	n.1422+6286C>T		intron_variant	Intron 9 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000444265.6	n.1061+6286C>T		intron_variant	Intron 7 of 10	1
CASC15	ENST00000606851.5	n.1391+6286C>T		intron_variant	Intron 9 of 11	2
CASC15	ENST00000607048.5	n.1138+3169C>T		intron_variant	Intron 9 of 11	2

Frequencies

GnomAD3 genomes AF: 0.0392 AC: 5960 AN: 152054 Hom.: 204 Cov.: 32

Gnomad AFR AF: 0.0567

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0260

Gnomad ASJ AF: 0.00865

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.0213

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0237

Gnomad OTH AF: 0.0268

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

GnomAD4 genome AF: 0.0392 AC: 5965 AN: 152172 Hom.: 205 Cov.: 32 AF XY: 0.0406 AC XY: 3020 AN XY: 74356

African (AFR) AF: 0.0567 AC: 2353 AN: 41530

American (AMR) AF: 0.0259 AC: 396 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00865 AC: 30 AN: 3470

East Asian (EAS) AF: 0.101 AC: 523 AN: 5182

South Asian (SAS) AF: 0.149 AC: 717 AN: 4814

European-Finnish (FIN) AF: 0.0213 AC: 225 AN: 10574

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0237 AC: 1613 AN: 68014

Other (OTH) AF: 0.0260 AC: 55 AN: 2112

Alfa AF: 0.0286 Hom.: 201

Bravo AF: 0.0369

Asia WGS AF: 0.104 AC: 361 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.23
DANN	Benign	0.62
PhyloP100		-0.39
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3749995; hg19: chr6-22117435;