8-127415475-C-T

Position:

• chr8-127415475-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_117100.1(CASC8):​n.1176+5354G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 181,604 control chromosomes in the GnomAD database, including 26,394 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 0.51 (21314 hom., cov: 32)
  • Exomes 𝑓: 0.57 (5080 hom.)
• Consequence: CASC8 NR_117100.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.270

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASC8	NR_117100.1	n.1176+5354G>A		intron_variant, non_coding_transcript_variant
POU5F1B	NM_001395745.1	c.-392C>T		5_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASC8	ENST00000502082.5	n.1176+5354G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76903 AN: 151834 Hom.: 21311 Cov.: 32

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.644

Gnomad SAS AF: 0.594

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.591

Gnomad OTH AF: 0.554

GnomAD4 exome AF: 0.569 AC: 16866 AN: 29654 Hom.: 5080 Cov.: 2 AF XY: 0.573 AC XY: 8511 AN XY: 14856

Gnomad4 AFR exome AF: 0.238

Gnomad4 AMR exome AF: 0.590

Gnomad4 ASJ exome AF: 0.573

Gnomad4 EAS exome AF: 0.666

Gnomad4 SAS exome AF: 0.554

Gnomad4 FIN exome AF: 0.563

Gnomad4 NFE exome AF: 0.576

Gnomad4 OTH exome AF: 0.561

GnomAD4 genome AF: 0.506 AC: 76920 AN: 151950 Hom.: 21314 Cov.: 32 AF XY: 0.512 AC XY: 37996 AN XY: 74248

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.638

Gnomad4 ASJ AF: 0.585

Gnomad4 EAS AF: 0.644

Gnomad4 SAS AF: 0.594

Gnomad4 FIN AF: 0.573

Gnomad4 NFE AF: 0.591

Gnomad4 OTH AF: 0.557

Alfa AF: 0.536 Hom.: 6342

Bravo AF: 0.501

Asia WGS AF: 0.597 AC: 2076 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.4
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs4871022; hg19: chr8-128427720;