8-127075659-T-C

Variant names:

• chr8-127075659-T-C
• rs6470494
• ENST00000523510.1:n.350+1167A>G

Variant summary

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

The ENST00000523510.1(CASC19):​n.350+1167A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.717 in 152,040 control chromosomes in the GnomAD database, including 39,074 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 0.72 (39074 hom., cov: 32)
• Consequence: CASC19 ENST00000523510.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.113
• Publications: 20 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]

PCAT2 (HGNC:45089): (prostate cancer associated transcript 2)

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 (SAS) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000523510.1. 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
	PCAT2	NR_119373.1		n.350+1167A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC19	ENST00000523510.1	TSL:3	n.350+1167A>G		intron	N/A
	PCAT1	ENST00000645463.1		n.855+69041T>C		intron	N/A
	PCAT1	ENST00000646670.1		n.1064+61885T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.717 AC: 108913 AN: 151922 Hom.: 39059 Cov.: 32

Gnomad AFR AF: 0.701

Gnomad AMI AF: 0.874

Gnomad AMR AF: 0.725

Gnomad ASJ AF: 0.702

Gnomad EAS AF: 0.670

Gnomad SAS AF: 0.755

Gnomad FIN AF: 0.727

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.722

Gnomad OTH AF: 0.730

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

GnomAD4 genome AF: 0.717 AC: 108987 AN: 152040 Hom.: 39074 Cov.: 32 AF XY: 0.719 AC XY: 53389 AN XY: 74304

African (AFR) AF: 0.701 AC: 29070 AN: 41458

American (AMR) AF: 0.725 AC: 11067 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.702 AC: 2439 AN: 3472

East Asian (EAS) AF: 0.670 AC: 3464 AN: 5172

South Asian (SAS) AF: 0.754 AC: 3635 AN: 4820

European-Finnish (FIN) AF: 0.727 AC: 7681 AN: 10572

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.722 AC: 49088 AN: 67970

Other (OTH) AF: 0.729 AC: 1540 AN: 2112

Alfa AF: 0.719 Hom.: 47753

Bravo AF: 0.713

Asia WGS AF: 0.755 AC: 2626 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	3.7
DANN	Benign	0.87
PhyloP100		-0.11

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: rs6470494;

hg19: chr8-128087904;