rs9263800

Positions:

• chr6-31166822-G-A

Variant summary

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

The ENST00000606567.6(POU5F1):​c.-394C>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 0.154 in 1,226,902 control chromosomes in the GnomAD database, including 15,216 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 0.15 (1735 hom., cov: 32)
  • Exomes 𝑓: 0.16 (13481 hom.)
• Consequence: POU5F1 ENST00000606567.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.392

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POU5F1	NM_002701.6	c.406-775C>T		intron_variant		ENST00000259915.13	NP_002692.2
POU5F1	NM_001173531.3	c.-394C>T		5_prime_UTR_variant	1/5		NP_001167002.1
POU5F1	NM_001285986.2	c.-1183C>T		5_prime_UTR_variant	1/3		NP_001272915.1
POU5F1	NM_203289.6	c.-880C>T		5_prime_UTR_variant	1/4		NP_976034.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POU5F1	ENST00000259915.13	c.406-775C>T		intron_variant		1	NM_002701.6	ENSP00000259915	P1

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22135 AN: 151978 Hom.: 1727 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.0922

Gnomad EAS AF: 0.0722

Gnomad SAS AF: 0.0670

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.162

GnomAD4 exome AF: 0.155 AC: 167006 AN: 1074808 Hom.: 13481 Cov.: 32 AF XY: 0.153 AC XY: 78377 AN XY: 512754

Gnomad4 AFR exome AF: 0.157

Gnomad4 AMR exome AF: 0.110

Gnomad4 ASJ exome AF: 0.0914

Gnomad4 EAS exome AF: 0.0445

Gnomad4 SAS exome AF: 0.0730

Gnomad4 FIN exome AF: 0.107

Gnomad4 NFE exome AF: 0.165

Gnomad4 OTH exome AF: 0.145

GnomAD4 genome AF: 0.146 AC: 22180 AN: 152094 Hom.: 1735 Cov.: 32 AF XY: 0.143 AC XY: 10612 AN XY: 74354

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.0922

Gnomad4 EAS AF: 0.0724

Gnomad4 SAS AF: 0.0683

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.160

Alfa AF: 0.154 Hom.: 1294

Bravo AF: 0.147

Asia WGS AF: 0.101 AC: 353 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.47
DANN	Benign	0.66

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: rs9263800; hg19: chr6-31134599;