8-127417017-G-A

Position:

• chr8-127417017-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NR_117100.1(CASC8):​n.1176+3812C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. 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 0.0 (0 hom., cov: 28)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CASC8 NR_117100.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.358

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASC8	NR_117100.1	n.1176+3812C>T		intron_variant, non_coding_transcript_variant
POU5F1B	NM_001395745.1	c.*71G>A		3_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+3812C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151676 Hom.: 0 Cov.: 28 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1401624 Hom.: 0 Cov.: 40 AF XY: 0.00 AC XY: 0 AN XY: 691588

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 151676 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 74050

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.0
DANN	Benign	0.93

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: rs9297754; hg19: chr8-128429262;