rs182632506

Variant names:

• chr8-127416221-C-A
• rs182632506
• NM_001159542.3:c.355C>A

Your query was ambiguous. Multiple possible variants found:

• chr8-127416221-C-A
• chr8-127416221-C-G
• chr8-127416221-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001159542.3(POU5F1B):​c.355C>A​(p.Pro119Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000886 in 1,613,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P119A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000088 (0 hom.)
• Consequence: POU5F1B NM_001159542.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.148
• Publications: 2 publications found

Genes affected

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]

CASC8 (HGNC:45129): (cancer susceptibility 8)

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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.016524494).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POU5F1B	NM_001159542.3	c.355C>A	p.Pro119Thr	missense_variant	Exon 1 of 1	ENST00000696633.1	NP_001153014.1
POU5F1B	NM_001395745.1	c.355C>A	p.Pro119Thr	missense_variant	Exon 2 of 2		NP_001382674.1
CASC8	NR_117100.1	n.1176+4608G>T		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POU5F1B	ENST00000696633.1	c.355C>A	p.Pro119Thr	missense_variant	Exon 1 of 1		NM_001159542.3	ENSP00000512769.1

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152198 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000116 AC: 29 AN: 249086 AF XY: 0.000126

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000260

Gnomad ASJ exome AF: 0.000898

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000979

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000883 AC: 129 AN: 1461572 Hom.: 0 Cov.: 112 AF XY: 0.0000935 AC XY: 68 AN XY: 727072

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.000201 AC: 9 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.000612 AC: 16 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.000348 AC: 2 AN: 5748

European-Non Finnish (NFE) AF: 0.0000827 AC: 92 AN: 1111806

Other (OTH) AF: 0.000149 AC: 9 AN: 60372

GnomAD4 genome AF: 0.0000919 AC: 14 AN: 152316 Hom.: 0 Cov.: 33 AF XY: 0.0000806 AC XY: 6 AN XY: 74472

African (AFR) AF: 0.0000241 AC: 1 AN: 41564

American (AMR) AF: 0.000261 AC: 4 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68028

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000256 Hom.: 0

Bravo AF: 0.0000945

ExAC AF: 0.000124 AC: 15

EpiCase AF: 0.000218

EpiControl AF: 0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	1.5
DANN	Benign	0.88
DEOGEN2	Benign	0.0054	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0014	N
LIST_S2	Benign	0.24	.;T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.017	T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	0.69	N;N
PhyloP100		-0.15
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.13	.;N
REVEL	Benign	0.12
Sift	Benign	0.14	.;T
Sift4G	Benign	0.39	.;T
Polyphen		0.0	B;B
Vest4		0.018
MVP		0.29
MPC		0.043
ClinPred		0.014	T
GERP RS		0.21
Varity_R		0.042
gMVP		0.20
Mutation Taster		=96/4	polymorphism

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: rs182632506; hg19: chr8-128428466;