8-127180736-A-G

Variant names:

• chr8-127180736-A-G
• rs2456449
• ENST00000641001.1:n.1438+4091T>C

Variant summary

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

The ENST00000641001.1(CASC19):​n.1438+4091T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 151,558 control chromosomes in the GnomAD database, including 7,308 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 0.30 (7308 hom., cov: 28)
• Consequence: CASC19 ENST00000641001.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.163
• Publications: 59 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 (EAS) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000641001.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC19	ENST00000641001.1		n.1438+4091T>C		intron	N/A
	CASC19	ENST00000641013.1		n.427-6372T>C		intron	N/A
	CASC19	ENST00000641029.1		n.463-6372T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45455 AN: 151444 Hom.: 7296 Cov.: 28

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.300 AC: 45484 AN: 151558 Hom.: 7308 Cov.: 28 AF XY: 0.300 AC XY: 22232 AN XY: 74036

African (AFR) AF: 0.194 AC: 7992 AN: 41286

American (AMR) AF: 0.345 AC: 5252 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1071 AN: 3464

East Asian (EAS) AF: 0.441 AC: 2270 AN: 5152

South Asian (SAS) AF: 0.287 AC: 1375 AN: 4794

European-Finnish (FIN) AF: 0.309 AC: 3227 AN: 10448

Middle Eastern (MID) AF: 0.240 AC: 70 AN: 292

European-Non Finnish (NFE) AF: 0.343 AC: 23292 AN: 67890

Other (OTH) AF: 0.302 AC: 634 AN: 2100

Alfa AF: 0.336 Hom.: 33813

Bravo AF: 0.301

Asia WGS AF: 0.398 AC: 1382 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.9
DANN	Benign	0.59
PhyloP100		0.16

Splicing

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

Other links and lift over

dbSNP: rs2456449; hg19: chr8-128192981;