ENST00000500112.3:n.463-459A>G

Variant names:

• chr8-127210176-T-C
• rs1948915
• ENST00000500112.3:n.463-459A>G

Variant summary

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

The ENST00000500112.3(CASC19):​n.463-459A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 152,088 control chromosomes in the GnomAD database, including 15,476 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 0.42 (15476 hom., cov: 32)
• Consequence: CASC19 ENST00000500112.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.134
• Publications: 14 publications found

Genes affected

CASC19 (HGNC:49476): (cancer susceptibility 19)

PCAT1 (HGNC:43022): (prostate cancer associated transcript 1) This gene produces a long non-coding RNA that promotes cell proliferation and is upregulated in prostate, colorectal, and other cancers. This RNA negatively regulates the BRCA2 tumor suppressor protein and positively regulates Myc oncoprotein. It contains binding sites for microRNAs, and may act as a sponge for microRNAs that regulate cell growth pathways. [provided by RefSeq, Dec 2017]

CCAT1 (HGNC:45128): (colon cancer associated transcript 1) This gene produces a long non-coding RNA that promotes tumor formation and is upregulated in colon cancer and other cancer cell types. This transcript may regulate long range chromosomal interactions, including at the Myc oncoprotein locus. This RNA may also function as a molecular sponge for microRNAs. [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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCAT1	NR_108049.1	n.460-459A>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC19	ENST00000500112.3	n.463-459A>G		intron_variant	Intron 1 of 1	1
CASC19	ENST00000641001.1	n.155-6956A>G		intron_variant	Intron 1 of 7
CASC19	ENST00000641029.1	n.161-6956A>G		intron_variant	Intron 1 of 6

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64381 AN: 151970 Hom.: 15425 Cov.: 32

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.529

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.405

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

GnomAD4 genome AF: 0.424 AC: 64492 AN: 152088 Hom.: 15476 Cov.: 32 AF XY: 0.423 AC XY: 31439 AN XY: 74376

African (AFR) AF: 0.654 AC: 27093 AN: 41454

American (AMR) AF: 0.345 AC: 5266 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 870 AN: 3472

East Asian (EAS) AF: 0.529 AC: 2738 AN: 5180

South Asian (SAS) AF: 0.368 AC: 1776 AN: 4826

European-Finnish (FIN) AF: 0.356 AC: 3765 AN: 10574

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.321 AC: 21858 AN: 68000

Other (OTH) AF: 0.410 AC: 862 AN: 2104

Alfa AF: 0.337 Hom.: 4735

Bravo AF: 0.434

Asia WGS AF: 0.506 AC: 1757 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.9
DANN	Benign	0.81
PhyloP100		0.13

Splicing

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

Other links and lift over

dbSNP: rs1948915; hg19: chr8-128222421; COSMIC: COSV72312928;