rs1456305

chr8-127115007-G-Achr8-127115007-G-T

Variant summary

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

The ENST00000642100.1(CASC19):n.418-35874C>T 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 0.879 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, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.205

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASC19	ENST00000642100.1	n.418-35874C>T		intron_variant, non_coding_transcript_variant
PCAT1	ENST00000645463.1	n.855+108389G>A		intron_variant, non_coding_transcript_variant
PCAT1	ENST00000646670.1	n.1064+101233G>A		intron_variant, non_coding_transcript_variant
PCAT1	ENST00000647190.2	n.1191+65707G>A		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.898

Gnomad4 AMR AF: 0.829

Gnomad4 ASJ AF: 0.817

Gnomad4 EAS AF: 0.971

Gnomad4 SAS AF: 0.857

Gnomad4 FIN AF: 0.833

Gnomad4 NFE AF: 0.883

Gnomad4 OTH AF: 0.876

Alfa AF: 0.873 Hom.: 78188

Bravo AF: 0.878

Asia WGS AF: 0.899 AC: 3128 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.098
Dann	Benign	0.30

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1456305; hg19: chr8-128127252;