chr6-22285845-G-A

Variant names:

• chr6-22285845-G-A
• rs10946545
• ENST00000561912.3:n.459-5033G>A

Variant summary

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

The ENST00000561912.3(CASC15):​n.459-5033G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0594 in 152,110 control chromosomes in the GnomAD database, including 406 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 0.059 (406 hom., cov: 32)
• Consequence: CASC15 ENST00000561912.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.534
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000561912.3	n.459-5033G>A		intron_variant	Intron 3 of 10	5
CASC15	ENST00000651569.1	n.376-5014G>A		intron_variant	Intron 3 of 7

Frequencies

GnomAD3 genomes AF: 0.0594 AC: 9028 AN: 151992 Hom.: 407 Cov.: 32

Gnomad AFR AF: 0.0252

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.0860

Gnomad ASJ AF: 0.0678

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.0992

Gnomad FIN AF: 0.0280

Gnomad MID AF: 0.0573

Gnomad NFE AF: 0.0623

Gnomad OTH AF: 0.0561

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

GnomAD4 genome AF: 0.0594 AC: 9028 AN: 152110 Hom.: 406 Cov.: 32 AF XY: 0.0611 AC XY: 4541 AN XY: 74340

African (AFR) AF: 0.0251 AC: 1042 AN: 41522

American (AMR) AF: 0.0862 AC: 1317 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0678 AC: 235 AN: 3468

East Asian (EAS) AF: 0.233 AC: 1199 AN: 5140

South Asian (SAS) AF: 0.0993 AC: 477 AN: 4804

European-Finnish (FIN) AF: 0.0280 AC: 297 AN: 10594

Middle Eastern (MID) AF: 0.0651 AC: 19 AN: 292

European-Non Finnish (NFE) AF: 0.0623 AC: 4234 AN: 67992

Other (OTH) AF: 0.0565 AC: 119 AN: 2106

Alfa AF: 0.0476 Hom.: 135

Bravo AF: 0.0616

Asia WGS AF: 0.165 AC: 574 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.9
DANN	Benign	0.39
PhyloP100		-0.53

Splicing

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

Other links and lift over

dbSNP: rs10946545; hg19: chr6-22286074;