chr8-127398703-C-G

Variant names:

• chr8-127398703-C-G
• rs12682374
• ENST00000501396.6:n.546+22126G>C

Variant summary

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

The ENST00000501396.6(CASC8):​n.546+22126G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 152,048 control chromosomes in the GnomAD database, including 14,218 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 0.40 (14218 hom., cov: 32)
• Consequence: CASC8 ENST00000501396.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.432
• Publications: 16 publications found

Genes affected

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

POU5F1B (HGNC:9223): (POU class 5 homeobox 1B) This intronless gene was thought to be a transcribed pseudogene of POU class 5 homeobox 1, however, it has been reported that this gene can encode a functional protein. The encoded protein is nearly the same length as and highly similar to the POU class 5 homeobox 1 transcription factor, has been shown to be a weak transcriptional activator and may play a role in carcinogenesis and eye development. [provided by RefSeq, Apr 2009]

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC8	NR_117100.1	n.1176+22126G>C		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000501396.6	n.546+22126G>C		intron_variant	Intron 1 of 2	1
CASC8	ENST00000502082.5	n.1176+22126G>C		intron_variant	Intron 5 of 5	1
CASC8	ENST00000523825.3	n.546+22126G>C		intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60382 AN: 151930 Hom.: 14215 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.369

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.429

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

GnomAD4 genome AF: 0.397 AC: 60382 AN: 152048 Hom.: 14218 Cov.: 32 AF XY: 0.402 AC XY: 29900 AN XY: 74304

African (AFR) AF: 0.135 AC: 5621 AN: 41504

American (AMR) AF: 0.449 AC: 6867 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1775 AN: 3468

East Asian (EAS) AF: 0.597 AC: 3085 AN: 5164

South Asian (SAS) AF: 0.506 AC: 2442 AN: 4824

European-Finnish (FIN) AF: 0.502 AC: 5293 AN: 10540

Middle Eastern (MID) AF: 0.452 AC: 132 AN: 292

European-Non Finnish (NFE) AF: 0.499 AC: 33916 AN: 67952

Other (OTH) AF: 0.434 AC: 916 AN: 2112

Alfa AF: 0.300 Hom.: 837

Bravo AF: 0.378

Asia WGS AF: 0.514 AC: 1786 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.73
DANN	Benign	0.40
PhyloP100		-0.43

Splicing

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

Other links and lift over

dbSNP: rs12682374; hg19: chr8-128410948;