8-127198984-T-C

Variant names:

• chr8-127198984-T-C
• rs2466035
• ENST00000641001.1:n.323+3058A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000641001.1(CASC19):​n.323+3058A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 152,078 control chromosomes in the GnomAD database, including 15,307 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 0.42 (15307 hom., cov: 32)
• Consequence: CASC19 ENST00000641001.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.638
• Publications: 18 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000641001.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC19	ENST00000641001.1		n.323+3058A>G		intron	N/A
	CASC19	ENST00000641013.1		n.255+3058A>G		intron	N/A
	CASC19	ENST00000641029.1		n.218+4179A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63812 AN: 151960 Hom.: 15282 Cov.: 32

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.390

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

GnomAD4 genome AF: 0.420 AC: 63903 AN: 152078 Hom.: 15307 Cov.: 32 AF XY: 0.415 AC XY: 30835 AN XY: 74368

African (AFR) AF: 0.664 AC: 27525 AN: 41442

American (AMR) AF: 0.395 AC: 6038 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 992 AN: 3472

East Asian (EAS) AF: 0.422 AC: 2186 AN: 5180

South Asian (SAS) AF: 0.266 AC: 1281 AN: 4822

European-Finnish (FIN) AF: 0.276 AC: 2921 AN: 10590

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.321 AC: 21791 AN: 67982

Other (OTH) AF: 0.392 AC: 827 AN: 2108

Alfa AF: 0.348 Hom.: 30816

Bravo AF: 0.441

Asia WGS AF: 0.430 AC: 1492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.1
DANN	Benign	0.57
PhyloP100		-0.64

Splicing

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

Other links and lift over

dbSNP: rs2466035; hg19: chr8-128211229; COSMIC: COSV107543385;