rs10087719

Variant names:

• chr8-127216618-A-G
• rs10087719
• ENST00000500112.2:n.429+2192T>C

Variant summary

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

The ENST00000500112.2(CASC19):​n.429+2192T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,184 control chromosomes in the GnomAD database, including 3,912 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 0.20 (3912 hom., cov: 32)
• Consequence: CASC19 ENST00000500112.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.309

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]

CCAT1 (HGNC:45128): (colon cancer associated transcript 1) This gene produces a long non-coding RNA that promotes tumor formation and is upregulated in colon cancer and other cancer cell types. This transcript may regulate long range chromosomal interactions, including at the Myc oncoprotein locus. This RNA may also function as a molecular sponge for microRNAs. [provided by RefSeq, Dec 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCAT1	NR_108049.1	n.459+2192T>C		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC19	ENST00000500112.2	n.429+2192T>C		intron_variant	Intron 1 of 1	1
CASC19	ENST00000641001.1	n.154+2197T>C		intron_variant	Intron 1 of 7
CASC19	ENST00000641029.1	n.160+2192T>C		intron_variant	Intron 1 of 6

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30940 AN: 152066 Hom.: 3915 Cov.: 32

Gnomad AFR AF: 0.0521

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.203 AC: 30940 AN: 152184 Hom.: 3912 Cov.: 32 AF XY: 0.202 AC XY: 15061 AN XY: 74398

Gnomad4 AFR AF: 0.0520

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.212

Gnomad4 EAS AF: 0.197

Gnomad4 SAS AF: 0.249

Gnomad4 FIN AF: 0.259

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.215

Alfa AF: 0.262 Hom.: 10333

Bravo AF: 0.195

Asia WGS AF: 0.211 AC: 733 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.4
DANN	Benign	0.84

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10087719; hg19: chr8-128228863;