rs1207774

Variant names:

• chr6-22038297-A-G
• rs1207774
• ENST00000444265.6:n.521+17755A>G

Variant summary

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

The ENST00000444265.6(CASC15):​n.521+17755A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,132 control chromosomes in the GnomAD database, including 3,903 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 0.19 (3903 hom., cov: 32)
• Consequence: CASC15 ENST00000444265.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0500
• Publications: 4 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 (AFR) allele frequency at 95% confidence interval = 0.389 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.1103+17755A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC15	ENST00000444265.6	TSL:1	n.521+17755A>G		intron	N/A
	CASC15	ENST00000606851.5	TSL:2	n.1072+17755A>G		intron	N/A
	CASC15	ENST00000607048.5	TSL:2	n.698+17755A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28164 AN: 152014 Hom.: 3898 Cov.: 32

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.0488

Gnomad FIN AF: 0.0881

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.185 AC: 28201 AN: 152132 Hom.: 3903 Cov.: 32 AF XY: 0.181 AC XY: 13467 AN XY: 74392

African (AFR) AF: 0.394 AC: 16334 AN: 41464

American (AMR) AF: 0.121 AC: 1857 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 489 AN: 3472

East Asian (EAS) AF: 0.146 AC: 756 AN: 5176

South Asian (SAS) AF: 0.0486 AC: 234 AN: 4816

European-Finnish (FIN) AF: 0.0881 AC: 934 AN: 10606

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7131 AN: 67988

Other (OTH) AF: 0.175 AC: 370 AN: 2110

Alfa AF: 0.131 Hom.: 3432

Bravo AF: 0.201

Asia WGS AF: 0.126 AC: 439 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	1.9
DANN	Benign	0.68
PhyloP100		-0.050

Splicing

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

Other links and lift over

dbSNP: rs1207774; hg19: chr6-22038526;