rs13274084

Variant names:

• chr8-127416506-A-G
• rs13274084
• NM_001159542.3:c.640A>G

Variant summary

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

The NM_001159542.3(POU5F1B):​c.640A>G​(p.Asn214Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 1,608,496 control chromosomes in the GnomAD database, including 11,982 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.093 (837 hom., cov: 32)
  • Exomes 𝑓: 0.12 (11145 hom.)
• Consequence: POU5F1B NM_001159542.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.505
• Publications: 16 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014190674).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001159542.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU5F1B	NM_001159542.3	MANE Select	c.640A>G	p.Asn214Asp	missense	Exon 1 of 1	NP_001153014.1
	POU5F1B	NM_001395745.1		c.640A>G	p.Asn214Asp	missense	Exon 2 of 2	NP_001382674.1
	CASC8	NR_117100.1		n.1176+4323T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU5F1B	ENST00000696633.1	MANE Select	c.640A>G	p.Asn214Asp	missense	Exon 1 of 1	ENSP00000512769.1
	CASC8	ENST00000501396.6	TSL:1	n.546+4323T>C		intron	N/A
	CASC8	ENST00000502082.5	TSL:1	n.1176+4323T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0927 AC: 14101 AN: 152042 Hom.: 837 Cov.: 32

Gnomad AFR AF: 0.0212

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.0802

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.0622

Gnomad SAS AF: 0.0711

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.107

GnomAD2 exomes AF: 0.108 AC: 25886 AN: 238938 AF XY: 0.109

Gnomad AFR exome AF: 0.0172

Gnomad AMR exome AF: 0.0563

Gnomad ASJ exome AF: 0.201

Gnomad EAS exome AF: 0.0665

Gnomad FIN exome AF: 0.167

Gnomad NFE exome AF: 0.134

Gnomad OTH exome AF: 0.130

GnomAD4 exome AF: 0.119 AC: 173375 AN: 1456336 Hom.: 11145 Cov.: 113 AF XY: 0.118 AC XY: 85376 AN XY: 723812

African (AFR) AF: 0.0199 AC: 667 AN: 33436

American (AMR) AF: 0.0594 AC: 2609 AN: 43932

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 5058 AN: 25964

East Asian (EAS) AF: 0.0784 AC: 3107 AN: 39650

South Asian (SAS) AF: 0.0699 AC: 5962 AN: 85272

European-Finnish (FIN) AF: 0.168 AC: 8925 AN: 53120

Middle Eastern (MID) AF: 0.165 AC: 936 AN: 5682

European-Non Finnish (NFE) AF: 0.125 AC: 138936 AN: 1109060

Other (OTH) AF: 0.119 AC: 7175 AN: 60220

GnomAD4 genome AF: 0.0927 AC: 14100 AN: 152160 Hom.: 837 Cov.: 32 AF XY: 0.0932 AC XY: 6929 AN XY: 74372

African (AFR) AF: 0.0212 AC: 882 AN: 41552

American (AMR) AF: 0.0799 AC: 1223 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 676 AN: 3468

East Asian (EAS) AF: 0.0624 AC: 322 AN: 5162

South Asian (SAS) AF: 0.0718 AC: 346 AN: 4822

European-Finnish (FIN) AF: 0.165 AC: 1746 AN: 10558

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8553 AN: 67984

Other (OTH) AF: 0.106 AC: 223 AN: 2106

Alfa AF: 0.124 Hom.: 409

Bravo AF: 0.0843

TwinsUK AF: 0.118 AC: 438

ALSPAC AF: 0.120 AC: 462

ExAC AF: 0.106 AC: 12908

Asia WGS AF: 0.0550 AC: 198 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	10
DANN	Benign	0.91
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0080	N
LIST_S2	Benign	0.82	T
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		0.51
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.24
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.015	D
Polyphen		0.0020	B
Vest4		0.024
MPC		0.044
ClinPred		0.017	T
GERP RS		-2.3
Varity_R		0.30
gMVP		0.17
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: rs13274084; hg19: chr8-128428751; COSMIC: COSV66966695; COSMIC: COSV66966695;