8-127415816-A-G

Position:

• chr8-127415816-A-G

Variant summary

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

The NR_117100.1(CASC8):​n.1176+5013T>C 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 0.501 in 1,465,806 control chromosomes in the GnomAD database, including 187,860 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 0.45 (16732 hom., cov: 33)
  • Exomes 𝑓: 0.51 (171128 hom.)
• Consequence: CASC8 NR_117100.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.480

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=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASC8	NR_117100.1	n.1176+5013T>C		intron_variant, non_coding_transcript_variant
POU5F1B	NM_001395745.1	c.-51A>G		5_prime_UTR_variant	2/2		NP_001382674.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000502082.5	n.1176+5013T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68339 AN: 151990 Hom.: 16727 Cov.: 33

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.477

GnomAD4 exome AF: 0.507 AC: 665702 AN: 1313698 Hom.: 171128 Cov.: 48 AF XY: 0.509 AC XY: 325335 AN XY: 639210

Gnomad4 AFR exome AF: 0.235

Gnomad4 AMR exome AF: 0.609

Gnomad4 ASJ exome AF: 0.439

Gnomad4 EAS exome AF: 0.656

Gnomad4 SAS exome AF: 0.584

Gnomad4 FIN exome AF: 0.486

Gnomad4 NFE exome AF: 0.504

Gnomad4 OTH exome AF: 0.506

GnomAD4 genome AF: 0.449 AC: 68360 AN: 152108 Hom.: 16732 Cov.: 33 AF XY: 0.456 AC XY: 33934 AN XY: 74346

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.576

Gnomad4 ASJ AF: 0.438

Gnomad4 EAS AF: 0.646

Gnomad4 SAS AF: 0.570

Gnomad4 FIN AF: 0.496

Gnomad4 NFE AF: 0.510

Gnomad4 OTH AF: 0.481

Alfa AF: 0.499 Hom.: 32781

Bravo AF: 0.446

Asia WGS AF: 0.585 AC: 2033 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	12
DANN	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs4871789; hg19: chr8-128428061; COSMIC: COSV66966705; COSMIC: COSV66966705;