8-127294819-C-T

Variant names:

• chr8-127294819-C-T
• rs11994592
• ENST00000501396.6:n.687-4759G>A

Variant summary

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

The ENST00000501396.6(CASC8):​n.687-4759G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0526 in 152,264 control chromosomes in the GnomAD database, including 454 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 0.053 (454 hom., cov: 32)
• Consequence: CASC8 ENST00000501396.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.241
• Publications: 2 publications found

Genes affected

CASC8 (HGNC:45129): (cancer susceptibility 8)

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]

CASC21 (HGNC:49836): (cancer susceptibility 21)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC21	NR_117099.1	n.149-27254C>T		intron_variant	Intron 1 of 3
CASC8	NR_117100.1	n.1177-4759G>A		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000501396.6	n.687-4759G>A		intron_variant	Intron 2 of 2	1
CASC8	ENST00000502082.5	n.1177-4759G>A		intron_variant	Intron 5 of 5	1
CASC8	ENST00000523825.3	n.547-4759G>A		intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes AF: 0.0526 AC: 7997 AN: 152146 Hom.: 452 Cov.: 32

Gnomad AFR AF: 0.0797

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.0413

Gnomad ASJ AF: 0.0351

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.0439

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0175

Gnomad OTH AF: 0.0531

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

GnomAD4 genome AF: 0.0526 AC: 8004 AN: 152264 Hom.: 454 Cov.: 32 AF XY: 0.0565 AC XY: 4209 AN XY: 74468

African (AFR) AF: 0.0795 AC: 3303 AN: 41548

American (AMR) AF: 0.0416 AC: 636 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0351 AC: 122 AN: 3472

East Asian (EAS) AF: 0.305 AC: 1575 AN: 5172

South Asian (SAS) AF: 0.106 AC: 512 AN: 4832

European-Finnish (FIN) AF: 0.0439 AC: 466 AN: 10618

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0175 AC: 1188 AN: 68012

Other (OTH) AF: 0.0530 AC: 112 AN: 2114

Alfa AF: 0.0296 Hom.: 173

Bravo AF: 0.0558

Asia WGS AF: 0.192 AC: 664 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	12
DANN	Benign	0.53
PhyloP100		0.24

Splicing

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

Other links and lift over

dbSNP: rs11994592; hg19: chr8-128307064;