8-127110414-C-T

Variant names:

• chr8-127110414-C-T
• rs1378897
• ENST00000642100.1:n.418-31281G>A

Variant summary

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

The ENST00000642100.1(CASC19):​n.418-31281G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0606 in 152,188 control chromosomes in the GnomAD database, including 445 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 0.061 (445 hom., cov: 32)
• Consequence: CASC19 ENST00000642100.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.167
• Publications: 9 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.181 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
CASC19	ENST00000642100.1	n.418-31281G>A		intron_variant	Intron 1 of 1
PCAT1	ENST00000645463.1	n.855+103796C>T		intron_variant	Intron 6 of 6
PCAT1	ENST00000646670.1	n.1064+96640C>T		intron_variant	Intron 5 of 6

Frequencies

GnomAD3 genomes AF: 0.0606 AC: 9219 AN: 152070 Hom.: 444 Cov.: 32

Gnomad AFR AF: 0.0134

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0927

Gnomad ASJ AF: 0.0608

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.0694

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0644

Gnomad OTH AF: 0.0701

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

GnomAD4 genome AF: 0.0606 AC: 9215 AN: 152188 Hom.: 445 Cov.: 32 AF XY: 0.0635 AC XY: 4723 AN XY: 74408

African (AFR) AF: 0.0134 AC: 555 AN: 41544

American (AMR) AF: 0.0927 AC: 1416 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0608 AC: 211 AN: 3470

East Asian (EAS) AF: 0.191 AC: 991 AN: 5182

South Asian (SAS) AF: 0.154 AC: 743 AN: 4820

European-Finnish (FIN) AF: 0.0694 AC: 734 AN: 10574

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0644 AC: 4380 AN: 68008

Other (OTH) AF: 0.0708 AC: 149 AN: 2106

Alfa AF: 0.0656 Hom.: 369

Bravo AF: 0.0574

Asia WGS AF: 0.153 AC: 532 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	5.0
DANN	Benign	0.31
PhyloP100		-0.17

Splicing

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

Other links and lift over

dbSNP: rs1378897; hg19: chr8-128122659;