chr6-22504519-A-C

Variant names:

• chr6-22504519-A-C
• rs2000191
• ENST00000652081.2:n.146-69600A>C

Variant summary

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

The ENST00000652081.2(CASC15):​n.146-69600A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0523 in 152,266 control chromosomes in the GnomAD database, including 261 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 0.052 (261 hom., cov: 32)
• Consequence: CASC15 ENST00000652081.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0150
• Publications: 3 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]

LOC105374971 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105374971	XR_001744024.2	n.483-13166A>C		intron_variant	Intron 3 of 4
LOC105374971	XR_001744025.1	n.403-13166A>C		intron_variant	Intron 4 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000652081.2	n.146-69600A>C		intron_variant	Intron 2 of 7
CASC15	ENST00000846434.1	n.347-13166A>C		intron_variant	Intron 2 of 5
CASC15	ENST00000846435.1	n.352-13166A>C		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0523 AC: 7958 AN: 152148 Hom.: 261 Cov.: 32

Gnomad AFR AF: 0.0224

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.0613

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.0208

Gnomad SAS AF: 0.0734

Gnomad FIN AF: 0.0588

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0647

Gnomad OTH AF: 0.0554

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

GnomAD4 genome AF: 0.0523 AC: 7961 AN: 152266 Hom.: 261 Cov.: 32 AF XY: 0.0521 AC XY: 3879 AN XY: 74448

African (AFR) AF: 0.0225 AC: 934 AN: 41584

American (AMR) AF: 0.0613 AC: 936 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 356 AN: 3470

East Asian (EAS) AF: 0.0210 AC: 109 AN: 5188

South Asian (SAS) AF: 0.0730 AC: 352 AN: 4822

European-Finnish (FIN) AF: 0.0588 AC: 623 AN: 10594

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0647 AC: 4401 AN: 68008

Other (OTH) AF: 0.0548 AC: 116 AN: 2116

Alfa AF: 0.0612 Hom.: 526

Bravo AF: 0.0515

Asia WGS AF: 0.0590 AC: 206 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.47
PhyloP100		0.015

Splicing

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

Other links and lift over

dbSNP: rs2000191; hg19: chr6-22504748;