8-127196124-A-G

Variant names:

• chr8-127196124-A-G
• rs138042437
• ENST00000641001.1:n.323+5918T>C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NR_120364.1(CASC19):​n.153+1351T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00395 in 152,364 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.0040 (2 hom., cov: 32)
• Consequence: CASC19 NR_120364.1 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -1.32

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS2: High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC19	NR_120364.1	n.153+1351T>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC19	ENST00000641001.1	n.323+5918T>C		intron_variant	Intron 3 of 7
CASC19	ENST00000641013.1	n.255+5918T>C		intron_variant	Intron 3 of 8
CASC19	ENST00000641029.1	n.219-6142T>C		intron_variant	Intron 2 of 6

Frequencies

GnomAD3 genomes AF: 0.00395 AC: 602 AN: 152246 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000675

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.0149

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00578

Gnomad OTH AF: 0.000478

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

GnomAD4 genome AF: 0.00395 AC: 602 AN: 152364 Hom.: 2 Cov.: 32 AF XY: 0.00416 AC XY: 310 AN XY: 74508

Gnomad4 AFR AF: 0.000673

Gnomad4 AMR AF: 0.000915

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.0149

Gnomad4 NFE AF: 0.00578

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00521 Hom.: 0

Bravo AF: 0.00284

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Familial prostate cancer Other:1

-

University of Washington Center for Mendelian Genomics, University of Washington

Significance: association

Review Status: no assertion criteria provided

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.052
DANN	Benign	0.54

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs138042437; hg19: chr8-128208369;