rs6983561

Variant names:

• chr8-127094635-A-C
• rs6983561
• ENST00000642100.1:n.418-15502T>G

Variant summary

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

The ENST00000642100.1(CASC19):​n.418-15502T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,164 control chromosomes in the GnomAD database, including 4,774 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 (4774 hom., cov: 32)
• Consequence: CASC19 ENST00000642100.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.738
• Publications: 99 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC19	ENST00000642100.1	n.418-15502T>G		intron_variant	Intron 1 of 1
PCAT1	ENST00000645463.1	n.855+88017A>C		intron_variant	Intron 6 of 6
PCAT1	ENST00000646670.1	n.1064+80861A>C		intron_variant	Intron 5 of 6

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24873 AN: 152046 Hom.: 4758 Cov.: 32

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0703

Gnomad ASJ AF: 0.0389

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0509

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0324

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.164 AC: 24938 AN: 152164 Hom.: 4774 Cov.: 32 AF XY: 0.161 AC XY: 11976 AN XY: 74410

African (AFR) AF: 0.458 AC: 18969 AN: 41444

American (AMR) AF: 0.0702 AC: 1074 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0389 AC: 135 AN: 3472

East Asian (EAS) AF: 0.244 AC: 1263 AN: 5176

South Asian (SAS) AF: 0.102 AC: 490 AN: 4818

European-Finnish (FIN) AF: 0.0509 AC: 541 AN: 10622

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0324 AC: 2202 AN: 68016

Other (OTH) AF: 0.117 AC: 248 AN: 2114

Alfa AF: 0.0749 Hom.: 5877

Bravo AF: 0.178

Asia WGS AF: 0.145 AC: 505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.2
DANN	Benign	0.40
PhyloP100		-0.74

Splicing

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

Other links and lift over

dbSNP: rs6983561; hg19: chr8-128106880;