rs7816475

Variant names:

• chr8-127213195-G-A
• rs7816475
• ENST00000500112.2:n.430-3478C>T

Variant summary

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

The ENST00000500112.2(CASC19):​n.430-3478C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,100 control chromosomes in the GnomAD database, including 3,622 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 0.22 (3622 hom., cov: 32)
• Consequence: CASC19 ENST00000500112.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCAT1	NR_108049.1	n.460-3478C>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC19	ENST00000500112.2	n.430-3478C>T		intron_variant	Intron 1 of 1	1
CASC19	ENST00000641001.1	n.154+5620C>T		intron_variant	Intron 1 of 7
CASC19	ENST00000641029.1	n.160+5615C>T		intron_variant	Intron 1 of 6

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32680 AN: 151982 Hom.: 3616 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.215 AC: 32716 AN: 152100 Hom.: 3622 Cov.: 32 AF XY: 0.212 AC XY: 15788 AN XY: 74382

Gnomad4 AFR AF: 0.214

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.132

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.205

Alfa AF: 0.228 Hom.: 2730

Bravo AF: 0.206

Asia WGS AF: 0.186 AC: 644 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	6.2
DANN	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7816475; hg19: chr8-128225440;