rs2466024

Positions:

• chr8-127175774-G-A

Variant summary

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

The ENST00000642100.1(CASC19):​n.417+9053C>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 0.46 in 152,108 control chromosomes in the GnomAD database, including 16,968 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 (16968 hom., cov: 33)
• Consequence: CASC19 ENST00000642100.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.106

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.611 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.417+9053C>T		intron_variant, non_coding_transcript_variant
PCAT1	ENST00000645463.1	n.856-117038G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69932 AN: 151988 Hom.: 16933 Cov.: 33

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.449

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

GnomAD4 genome AF: 0.460 AC: 70025 AN: 152108 Hom.: 16968 Cov.: 33 AF XY: 0.457 AC XY: 33967 AN XY: 74358

Gnomad4 AFR AF: 0.618

Gnomad4 AMR AF: 0.442

Gnomad4 ASJ AF: 0.358

Gnomad4 EAS AF: 0.518

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.397

Gnomad4 OTH AF: 0.450

Alfa AF: 0.410 Hom.: 12930

Bravo AF: 0.476

Asia WGS AF: 0.467 AC: 1623 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	1.3
DANN	Benign	0.52

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2466024; hg19: chr8-128188019;