8-127407262-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000645438.1(POU5F1B):​c.-559-7626C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0073 in 152,256 control chromosomes in the GnomAD database, including 36 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 0.0073 ( 36 hom., cov: 31)

Consequence

POU5F1B
ENST00000645438.1 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.984
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CASC8NR_117100.1 linkn.1176+13567G>A intron_variant Intron 5 of 5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CASC8ENST00000501396.5 linkn.546+13567G>A intron_variant Intron 1 of 2 1
CASC8ENST00000502082.5 linkn.1176+13567G>A intron_variant Intron 5 of 5 1
CASC8ENST00000523825.2 linkn.546+13567G>A intron_variant Intron 1 of 1 1

Frequencies

GnomAD3 genomes
AF:
0.00732
AC:
1114
AN:
152138
Hom.:
36
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000869
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000458
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.126
Gnomad SAS
AF:
0.00621
Gnomad FIN
AF:
0.0227
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00198
Gnomad OTH
AF:
0.00622
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.00730
AC:
1111
AN:
152256
Hom.:
36
Cov.:
31
AF XY:
0.00895
AC XY:
666
AN XY:
74450
show subpopulations
Gnomad4 AFR
AF:
0.000866
Gnomad4 AMR
AF:
0.000458
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.125
Gnomad4 SAS
AF:
0.00601
Gnomad4 FIN
AF:
0.0227
Gnomad4 NFE
AF:
0.00198
Gnomad4 OTH
AF:
0.00663
Alfa
AF:
0.00465
Hom.:
1
Bravo
AF:
0.00634
Asia WGS
AF:
0.0450
AC:
157
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
1.0
DANN
Benign
0.67

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs11986916; hg19: chr8-128419507; API