8-127115007-G-A

Variant names:

• chr8-127115007-G-A
• rs1456305
• ENST00000642100.1:n.418-35874C>T

Variant summary

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

The ENST00000642100.1(CASC19):​n.418-35874C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.879 in 152,176 control chromosomes in the GnomAD database, including 58,892 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 0.88 (58892 hom., cov: 31)
• Consequence: CASC19 ENST00000642100.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.205
• Publications: 8 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000642100.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC19	ENST00000642100.1		n.418-35874C>T		intron	N/A
	PCAT1	ENST00000645463.1		n.855+108389G>A		intron	N/A
	PCAT1	ENST00000646670.1		n.1064+101233G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.879 AC: 133635 AN: 152058 Hom.: 58859 Cov.: 31

Gnomad AFR AF: 0.899

Gnomad AMI AF: 0.916

Gnomad AMR AF: 0.829

Gnomad ASJ AF: 0.817

Gnomad EAS AF: 0.972

Gnomad SAS AF: 0.859

Gnomad FIN AF: 0.833

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.883

Gnomad OTH AF: 0.875

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

GnomAD4 genome AF: 0.879 AC: 133724 AN: 152176 Hom.: 58892 Cov.: 31 AF XY: 0.874 AC XY: 64997 AN XY: 74366

African (AFR) AF: 0.898 AC: 37302 AN: 41520

American (AMR) AF: 0.829 AC: 12663 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.817 AC: 2838 AN: 3472

East Asian (EAS) AF: 0.971 AC: 5040 AN: 5188

South Asian (SAS) AF: 0.857 AC: 4127 AN: 4816

European-Finnish (FIN) AF: 0.833 AC: 8805 AN: 10574

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.883 AC: 60035 AN: 68016

Other (OTH) AF: 0.876 AC: 1850 AN: 2112

Alfa AF: 0.874 Hom.: 110828

Bravo AF: 0.878

Asia WGS AF: 0.899 AC: 3128 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.098
DANN	Benign	0.30
PhyloP100		-0.20

Splicing

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

Other links and lift over

dbSNP: rs1456305; hg19: chr8-128127252;