rs3132526

Variant names:

• chr6-31166398-C-T
• rs3132526
• ENST00000471529.6:c.-534G>A

Variant summary

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

The ENST00000471529.6(POU5F1):​c.-534G>A variant causes a 5 prime UTR premature start codon gain 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_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
POU5F1	NM_002701.6	c.406-351G>A		intron_variant	Intron 1 of 4	ENST00000259915.13	NP_002692.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POU5F1	ENST00000259915.13	c.406-351G>A		intron_variant	Intron 1 of 4	1	NM_002701.6	ENSP00000259915.7

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

GnomAD2 exomes AF: 0.520 AC: 65344 AN: 125642 AF XY: 0.520

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 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

African (AFR) AF: 0.637 AC: 18308 AN: 28746

American (AMR) AF: 0.508 AC: 15633 AN: 30746

Ashkenazi Jewish (ASJ) AF: 0.628 AC: 13496 AN: 21492

East Asian (EAS) AF: 0.549 AC: 13553 AN: 24706

South Asian (SAS) AF: 0.506 AC: 38860 AN: 76796

European-Finnish (FIN) AF: 0.470 AC: 6464 AN: 13756

Middle Eastern (MID) AF: 0.563 AC: 2799 AN: 4972

European-Non Finnish (NFE) AF: 0.510 AC: 500094 AN: 980168

Other (OTH) AF: 0.534 AC: 26210 AN: 49092

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

African (AFR) AF: 0.632 AC: 26163 AN: 41428

American (AMR) AF: 0.545 AC: 8333 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.635 AC: 2203 AN: 3472

East Asian (EAS) AF: 0.563 AC: 2913 AN: 5172

South Asian (SAS) AF: 0.499 AC: 2406 AN: 4818

European-Finnish (FIN) AF: 0.453 AC: 4781 AN: 10548

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.504 AC: 34241 AN: 67970

Other (OTH) AF: 0.534 AC: 1127 AN: 2110

Alfa AF: 0.535 Hom.: 4186

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
PhyloP100		-1.3
PromoterAI		0.00020	Neutral
Mutation Taster		=299/1	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: rs3132526; hg19: chr6-31134175;