chr6-22282803-T-C

Variant names:

• chr6-22282803-T-C
• rs849872
• ENST00000561912.3:n.459-8075T>C

Variant summary

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

The ENST00000651569.1(CASC15):​n.376-8056T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 152,086 control chromosomes in the GnomAD database, including 4,511 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 0.23 (4511 hom., cov: 32)
• Consequence: CASC15 ENST00000651569.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.272
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000651569.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC15	ENST00000561912.3	TSL:5	n.459-8075T>C		intron	N/A
	CASC15	ENST00000651569.1		n.376-8056T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34802 AN: 151968 Hom.: 4500 Cov.: 32

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.0956

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.237

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

GnomAD4 genome AF: 0.229 AC: 34865 AN: 152086 Hom.: 4511 Cov.: 32 AF XY: 0.234 AC XY: 17390 AN XY: 74358

African (AFR) AF: 0.329 AC: 13633 AN: 41478

American (AMR) AF: 0.293 AC: 4483 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 631 AN: 3470

East Asian (EAS) AF: 0.308 AC: 1592 AN: 5168

South Asian (SAS) AF: 0.325 AC: 1565 AN: 4820

European-Finnish (FIN) AF: 0.176 AC: 1865 AN: 10576

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10438 AN: 67976

Other (OTH) AF: 0.237 AC: 502 AN: 2116

Alfa AF: 0.0768 Hom.: 114

Bravo AF: 0.241

Asia WGS AF: 0.318 AC: 1102 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.75
PhyloP100		-0.27

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs849872;

hg19: chr6-22283032;