8-127417476-T-C

Variant names:

• chr8-127417476-T-C
• rs6985419
• ENST00000501396.6:n.546+3353A>G

Variant summary

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

The ENST00000465342.4(POU5F1B):​c.*530T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 155,558 control chromosomes in the GnomAD database, including 31,557 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 0.63 (30791 hom., cov: 31)
  • Exomes 𝑓: 0.62 (766 hom.)
• Consequence: POU5F1B ENST00000465342.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000465342.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	NR_117100.1		n.1176+3353A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	ENST00000501396.6	TSL:1	n.546+3353A>G		intron	N/A
	CASC8	ENST00000502082.5	TSL:1	n.1176+3353A>G		intron	N/A
	CASC8	ENST00000523825.3	TSL:1	n.546+3353A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.633 AC: 95895 AN: 151572 Hom.: 30779 Cov.: 31

Gnomad AFR AF: 0.532

Gnomad AMI AF: 0.699

Gnomad AMR AF: 0.702

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.795

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.655

Gnomad OTH AF: 0.653

GnomAD4 exome AF: 0.619 AC: 2394 AN: 3868 Hom.: 766 Cov.: 0 AF XY: 0.640 AC XY: 1138 AN XY: 1778

African (AFR) AF: 0.509 AC: 54 AN: 106

American (AMR) AF: 0.648 AC: 57 AN: 88

Ashkenazi Jewish (ASJ) AF: 0.579 AC: 161 AN: 278

East Asian (EAS) AF: 0.738 AC: 540 AN: 732

South Asian (SAS) AF: 0.520 AC: 26 AN: 50

European-Finnish (FIN) AF: 0.875 AC: 7 AN: 8

Middle Eastern (MID) AF: 0.773 AC: 17 AN: 22

European-Non Finnish (NFE) AF: 0.588 AC: 1338 AN: 2274

Other (OTH) AF: 0.626 AC: 194 AN: 310

GnomAD4 genome AF: 0.632 AC: 95942 AN: 151690 Hom.: 30791 Cov.: 31 AF XY: 0.640 AC XY: 47410 AN XY: 74124

African (AFR) AF: 0.532 AC: 21997 AN: 41382

American (AMR) AF: 0.702 AC: 10722 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.615 AC: 2133 AN: 3470

East Asian (EAS) AF: 0.795 AC: 4107 AN: 5168

South Asian (SAS) AF: 0.666 AC: 3204 AN: 4808

European-Finnish (FIN) AF: 0.685 AC: 7124 AN: 10402

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.655 AC: 44432 AN: 67878

Other (OTH) AF: 0.655 AC: 1382 AN: 2110

Alfa AF: 0.646 Hom.: 121892

Bravo AF: 0.629

Asia WGS AF: 0.716 AC: 2487 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.8
DANN	Benign	0.62
PhyloP100		0.036
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6985419; hg19: chr8-128429721;