rs3132526

Positions:

• chr6-31166398-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000471529.6(POU5F1):​c.-534G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 1,382,474 control chromosomes in the GnomAD database, including 188,093 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 0.54 (22913 hom., cov: 33)
  • Exomes 𝑓: 0.52 (165180 hom.)
• Consequence: POU5F1 ENST00000471529.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25

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]

TCF19 (HGNC:11629): (transcription factor 19) This gene encodes a protein that contains a PHD-type zinc finger domain and likely functions as a transcription factor. The encoded protein plays a role proliferation and apoptosis of pancreatic beta cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POU5F1	NM_002701.6	c.406-351G>A		intron_variant		ENST00000259915.13
POU5F1	NM_001285986.2	c.-759G>A		5_prime_UTR_variant	1/3
POU5F1	NM_203289.6	c.-456G>A		5_prime_UTR_variant	1/4
POU5F1	NM_001173531.3	c.-106+136G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POU5F1	ENST00000259915.13	c.406-351G>A		intron_variant		1	NM_002701.6	P1

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82757 AN: 151882 Hom.: 22909 Cov.: 33

Gnomad AFR AF: 0.632

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.534

GnomAD3 exomes AF: 0.520 AC: 65344 AN: 125642 Hom.: 17462 AF XY: 0.520 AC XY: 35801 AN XY: 68846

Gnomad AFR exome AF: 0.638

Gnomad AMR exome AF: 0.503

Gnomad ASJ exome AF: 0.630

Gnomad EAS exome AF: 0.551

Gnomad SAS exome AF: 0.500

Gnomad FIN exome AF: 0.452

Gnomad NFE exome AF: 0.504

Gnomad OTH exome AF: 0.536

GnomAD4 exome AF: 0.516 AC: 635417 AN: 1230474 Hom.: 165180 Cov.: 42 AF XY: 0.516 AC XY: 310249 AN XY: 601390

Gnomad4 AFR exome AF: 0.637

Gnomad4 AMR exome AF: 0.508

Gnomad4 ASJ exome AF: 0.628

Gnomad4 EAS exome AF: 0.549

Gnomad4 SAS exome AF: 0.506

Gnomad4 FIN exome AF: 0.470

Gnomad4 NFE exome AF: 0.510

Gnomad4 OTH exome AF: 0.534

GnomAD4 genome AF: 0.545 AC: 82791 AN: 152000 Hom.: 22913 Cov.: 33 AF XY: 0.542 AC XY: 40245 AN XY: 74288

Gnomad4 AFR AF: 0.632

Gnomad4 AMR AF: 0.545

Gnomad4 ASJ AF: 0.635

Gnomad4 EAS AF: 0.563

Gnomad4 SAS AF: 0.499

Gnomad4 FIN AF: 0.453

Gnomad4 NFE AF: 0.504

Gnomad4 OTH AF: 0.534

Alfa AF: 0.532 Hom.: 4034

Bravo AF: 0.557

Asia WGS AF: 0.563 AC: 1956 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.41
DANN	Benign	0.63

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: rs3132526; hg19: chr6-31134175;