6-22110486-A-T

Variant names:

• chr6-22110486-A-T
• rs10484388
• ENST00000444265.6:n.888-261A>T

Variant summary

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

The ENST00000444265.6(CASC15):​n.888-261A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0401 in 152,282 control chromosomes in the GnomAD database, including 210 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 0.040 (210 hom., cov: 32)
• Consequence: CASC15 ENST00000444265.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.330
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000444265.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC15	NR_015410.2		n.1249-261A>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC15	ENST00000444265.6	TSL:1	n.888-261A>T		intron	N/A
	CASC15	ENST00000606851.5	TSL:2	n.1218-261A>T		intron	N/A
	CASC15	ENST00000607048.5	TSL:2	n.844-261A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0401 AC: 6099 AN: 152162 Hom.: 209 Cov.: 32

Gnomad AFR AF: 0.0590

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.0270

Gnomad ASJ AF: 0.00864

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.0218

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0240

Gnomad OTH AF: 0.0278

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

GnomAD4 genome AF: 0.0401 AC: 6104 AN: 152282 Hom.: 210 Cov.: 32 AF XY: 0.0414 AC XY: 3079 AN XY: 74456

African (AFR) AF: 0.0590 AC: 2450 AN: 41552

American (AMR) AF: 0.0269 AC: 411 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00864 AC: 30 AN: 3472

East Asian (EAS) AF: 0.108 AC: 560 AN: 5174

South Asian (SAS) AF: 0.140 AC: 675 AN: 4826

European-Finnish (FIN) AF: 0.0218 AC: 232 AN: 10620

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

European-Non Finnish (NFE) AF: 0.0240 AC: 1630 AN: 68018

Other (OTH) AF: 0.0270 AC: 57 AN: 2110

Alfa AF: 0.0272 Hom.: 9

Bravo AF: 0.0384

Asia WGS AF: 0.100 AC: 349 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.15
DANN	Benign	0.62
PhyloP100		-0.33
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: rs10484388; hg19: chr6-22110715;