chr8-127112950-C-T

Position:

• chr8-127112950-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000642100.1(CASC19):​n.418-33817G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,006 control chromosomes in the GnomAD database, including 4,306 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 0.16 (4306 hom., cov: 32)
• Consequence: CASC19 ENST00000642100.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASC19	ENST00000642100.1	n.418-33817G>A		intron_variant, non_coding_transcript_variant
PCAT1	ENST00000645463.1	n.855+106332C>T		intron_variant, non_coding_transcript_variant
PCAT1	ENST00000646670.1	n.1064+99176C>T		intron_variant, non_coding_transcript_variant
PCAT1	ENST00000647190.2	n.1191+63650C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23874 AN: 151888 Hom.: 4287 Cov.: 32

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0669

Gnomad ASJ AF: 0.0389

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0514

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0323

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.158 AC: 23943 AN: 152006 Hom.: 4306 Cov.: 32 AF XY: 0.155 AC XY: 11522 AN XY: 74308

Gnomad4 AFR AF: 0.435

Gnomad4 AMR AF: 0.0668

Gnomad4 ASJ AF: 0.0389

Gnomad4 EAS AF: 0.245

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.0514

Gnomad4 NFE AF: 0.0323

Gnomad4 OTH AF: 0.114

Alfa AF: 0.0569 Hom.: 1237

Bravo AF: 0.170

Asia WGS AF: 0.146 AC: 508 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.13
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10505483; hg19: chr8-128125195;