chr8-127191728-A-G

Position:

• chr8-127191728-A-G

Variant summary

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

The ENST00000641060.1(CASC19):​n.442T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 151,950 control chromosomes in the GnomAD database, including 17,657 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 0.46 (17657 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CASC19 ENST00000641060.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.749

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASC19	NR_120364.1	n.154-3613T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASC19	ENST00000641060.1	n.442T>C		non_coding_transcript_exon_variant	5/7
CASC19	ENST00000641674.2	n.538T>C		non_coding_transcript_exon_variant	5/9
CASC19	ENST00000642082.1	n.588T>C		non_coding_transcript_exon_variant	1/4

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69886 AN: 151830 Hom.: 17619 Cov.: 31

Gnomad AFR AF: 0.677

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.422

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 SAS exome AF: 0.00

GnomAD4 genome AF: 0.461 AC: 69977 AN: 151950 Hom.: 17657 Cov.: 31 AF XY: 0.454 AC XY: 33723 AN XY: 74248

Gnomad4 AFR AF: 0.677

Gnomad4 AMR AF: 0.426

Gnomad4 ASJ AF: 0.332

Gnomad4 EAS AF: 0.450

Gnomad4 SAS AF: 0.291

Gnomad4 FIN AF: 0.339

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.423

Alfa AF: 0.414 Hom.: 4163

Bravo AF: 0.479

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.3
DANN	Benign	0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1021955; hg19: chr8-128203973;