rs3130932

chr6-31166166-C-A

Variant summary

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

The ENST00000471529.6(POU5F1):c.-302G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.667 in 1,605,810 control chromosomes in the GnomAD database, including 359,770 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 0.69 (36761 hom., cov: 32)
  • Exomes 𝑓: 0.66 (323009 hom.)
• Consequence: POU5F1 ENST00000471529.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.495

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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POU5F1	NM_002701.6	c.406-119G>T		intron_variant		ENST00000259915.13
POU5F1	NM_001285986.2	c.-527G>T		5_prime_UTR_variant	1/3
POU5F1	NM_203289.6	c.-224G>T		5_prime_UTR_variant	1/4
POU5F1	NM_001173531.3	c.-105-119G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POU5F1	ENST00000259915.13	c.406-119G>T		intron_variant		1	NM_002701.6	P1

Frequencies

GnomAD3 genomes AF: 0.691 AC: 104957 AN: 151930 Hom.: 36731 Cov.: 32

Gnomad AFR AF: 0.792

Gnomad AMI AF: 0.633

Gnomad AMR AF: 0.679

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.635

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.695

GnomAD3 exomes AF: 0.646 AC: 152795 AN: 236422 Hom.: 49611 AF XY: 0.644 AC XY: 82612 AN XY: 128280

Gnomad AFR exome AF: 0.792

Gnomad AMR exome AF: 0.599

Gnomad ASJ exome AF: 0.719

Gnomad EAS exome AF: 0.654

Gnomad SAS exome AF: 0.579

Gnomad FIN exome AF: 0.577

Gnomad NFE exome AF: 0.664

Gnomad OTH exome AF: 0.672

GnomAD4 exome AF: 0.665 AC: 966642 AN: 1453762 Hom.: 323009 Cov.: 68 AF XY: 0.662 AC XY: 478343 AN XY: 722684

Gnomad4 AFR exome AF: 0.796

Gnomad4 AMR exome AF: 0.610

Gnomad4 ASJ exome AF: 0.718

Gnomad4 EAS exome AF: 0.601

Gnomad4 SAS exome AF: 0.583

Gnomad4 FIN exome AF: 0.578

Gnomad4 NFE exome AF: 0.674

Gnomad4 OTH exome AF: 0.675

GnomAD4 genome AF: 0.691 AC: 105036 AN: 152048 Hom.: 36761 Cov.: 32 AF XY: 0.685 AC XY: 50877 AN XY: 74318

Gnomad4 AFR AF: 0.792

Gnomad4 AMR AF: 0.679

Gnomad4 ASJ AF: 0.727

Gnomad4 EAS AF: 0.635

Gnomad4 SAS AF: 0.568

Gnomad4 FIN AF: 0.569

Gnomad4 NFE AF: 0.663

Gnomad4 OTH AF: 0.693

Alfa AF: 0.670 Hom.: 45806

Bravo AF: 0.705

Asia WGS AF: 0.665 AC: 2310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	13
Dann	Benign	0.83

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: rs3130932; hg19: chr6-31133943; COSMIC: COSV52562806; COSMIC: COSV52562806;