8-127160441-T-C

Variant names:

• chr8-127160441-T-C
• rs2124600
• ENST00000641421.1:n.600+1481A>G

Variant summary

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

The ENST00000641421.1(CASC19):​n.600+1481A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 152,012 control chromosomes in the GnomAD database, including 16,376 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 0.44 (16376 hom., cov: 32)
• Consequence: CASC19 ENST00000641421.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.493
• Publications: 6 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000641421.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

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

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC19	ENST00000641421.1		n.600+1481A>G		intron	N/A
	CASC19	ENST00000641425.1		n.689-7097A>G		intron	N/A
	CASC19	ENST00000641588.1		n.1072+1481A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67361 AN: 151894 Hom.: 16336 Cov.: 32

Gnomad AFR AF: 0.648

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.439

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

GnomAD4 genome AF: 0.444 AC: 67459 AN: 152012 Hom.: 16376 Cov.: 32 AF XY: 0.440 AC XY: 32698 AN XY: 74322

African (AFR) AF: 0.648 AC: 26844 AN: 41430

American (AMR) AF: 0.441 AC: 6733 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 1177 AN: 3468

East Asian (EAS) AF: 0.514 AC: 2649 AN: 5156

South Asian (SAS) AF: 0.308 AC: 1485 AN: 4822

European-Finnish (FIN) AF: 0.288 AC: 3041 AN: 10576

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.355 AC: 24148 AN: 67982

Other (OTH) AF: 0.439 AC: 928 AN: 2112

Alfa AF: 0.378 Hom.: 22369

Bravo AF: 0.465

Asia WGS AF: 0.455 AC: 1579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.63
DANN	Benign	0.42
PhyloP100		-0.49

Splicing

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

Other links and lift over

dbSNP: rs2124600; hg19: chr8-128172686;