rs1265160

Positions:

• chr6-31170594-G-A
• chr6-31170594-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002701.6(POU5F1):​c.27C>T​(p.Phe9=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 1,560,906 control chromosomes in the GnomAD database, including 14,651 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 0.14 (1715 hom., cov: 33)
  • Exomes 𝑓: 0.13 (12936 hom.)
• Consequence: POU5F1 NM_002701.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.49

Genes affected

POU5F1 (HGNC:9221): (POU class 5 homeobox 1) This gene encodes a transcription factor containing a POU homeodomain that plays a key role in embryonic development and stem cell pluripotency. Aberrant expression of this gene in adult tissues is associated with tumorigenesis. This gene can participate in a translocation with the Ewing's sarcoma gene on chromosome 21, which also leads to tumor formation. Alternative splicing, as well as usage of alternative AUG and non-AUG translation initiation codons, results in multiple isoforms. One of the AUG start codons is polymorphic in human populations. Related pseudogenes have been identified on chromosomes 1, 3, 8, 10, and 12. [provided by RefSeq, Oct 2013]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP7: Synonymous conserved (PhyloP=-2.49 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POU5F1	NM_002701.6	c.27C>T	p.Phe9=	synonymous_variant	1/5	ENST00000259915.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POU5F1	ENST00000259915.13	c.27C>T	p.Phe9=	synonymous_variant	1/5	1	NM_002701.6	P1
POU5F1	ENST00000441888.7	c.-183-4547C>T		intron_variant		1
POU5F1	ENST00000461401.1	n.65C>T		non_coding_transcript_exon_variant	1/2	1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21820 AN: 152032 Hom.: 1711 Cov.: 33

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.0637

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.0533

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.125

GnomAD3 exomes AF: 0.138 AC: 22752 AN: 164462 Hom.: 1913 AF XY: 0.132 AC XY: 11790 AN XY: 89154

Gnomad AFR exome AF: 0.144

Gnomad AMR exome AF: 0.209

Gnomad ASJ exome AF: 0.0476

Gnomad EAS exome AF: 0.284

Gnomad SAS exome AF: 0.102

Gnomad FIN exome AF: 0.132

Gnomad NFE exome AF: 0.111

Gnomad OTH exome AF: 0.122

GnomAD4 exome AF: 0.129 AC: 181581 AN: 1408756 Hom.: 12936 Cov.: 84 AF XY: 0.126 AC XY: 88020 AN XY: 696150

Gnomad4 AFR exome AF: 0.146

Gnomad4 AMR exome AF: 0.205

Gnomad4 ASJ exome AF: 0.0520

Gnomad4 EAS exome AF: 0.302

Gnomad4 SAS exome AF: 0.106

Gnomad4 FIN exome AF: 0.132

Gnomad4 NFE exome AF: 0.124

Gnomad4 OTH exome AF: 0.120

GnomAD4 genome AF: 0.144 AC: 21838 AN: 152150 Hom.: 1715 Cov.: 33 AF XY: 0.146 AC XY: 10854 AN XY: 74388

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.0533

Gnomad4 EAS AF: 0.303

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.128

Alfa AF: 0.116 Hom.: 388

Bravo AF: 0.149

Asia WGS AF: 0.206 AC: 715 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	4.1
DANN	Benign	0.92

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: rs1265160; hg19: chr6-31138371;