8-127100470-T-G

Variant names:

• chr8-127100470-T-G
• rs16901970
• ENST00000642100.1:n.418-21337A>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000642100.1(CASC19):​n.418-21337A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,148 control chromosomes in the GnomAD database, including 2,603 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 0.13 (2603 hom., cov: 32)
• Consequence: CASC19 ENST00000642100.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.877
• Publications: 11 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.324 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.418-21337A>C		intron_variant	Intron 1 of 1
PCAT1	ENST00000645463.1	n.855+93852T>G		intron_variant	Intron 6 of 6
PCAT1	ENST00000646670.1	n.1064+86696T>G		intron_variant	Intron 5 of 6

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19212 AN: 152030 Hom.: 2592 Cov.: 32

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0553

Gnomad ASJ AF: 0.0389

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.0508

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0319

Gnomad OTH AF: 0.0896

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

GnomAD4 genome AF: 0.127 AC: 19262 AN: 152148 Hom.: 2603 Cov.: 32 AF XY: 0.126 AC XY: 9344 AN XY: 74424

African (AFR) AF: 0.328 AC: 13612 AN: 41440

American (AMR) AF: 0.0552 AC: 845 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0389 AC: 135 AN: 3470

East Asian (EAS) AF: 0.244 AC: 1264 AN: 5176

South Asian (SAS) AF: 0.101 AC: 488 AN: 4818

European-Finnish (FIN) AF: 0.0508 AC: 539 AN: 10610

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0319 AC: 2172 AN: 68014

Other (OTH) AF: 0.0910 AC: 192 AN: 2110

Alfa AF: 0.0595 Hom.: 671

Bravo AF: 0.135

Asia WGS AF: 0.137 AC: 476 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	14
DANN	Benign	0.75
PhyloP100		0.88

Splicing

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

Other links and lift over

dbSNP: rs16901970; hg19: chr8-128112715;