rs11965454

chr6-31166814-T-C

Variant summary

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

The ENST00000606567.6(POU5F1):c.-386A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0393 in 1,187,126 control chromosomes in the GnomAD database, including 1,760 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 0.073 (678 hom., cov: 32)
  • Exomes 𝑓: 0.034 (1082 hom.)
• Consequence: POU5F1 ENST00000606567.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.253

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 (EAS) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POU5F1	NM_002701.6	c.406-767A>G		intron_variant		ENST00000259915.13
POU5F1	NM_001173531.3	c.-386A>G		5_prime_UTR_variant	1/5
POU5F1	NM_001285986.2	c.-1175A>G		5_prime_UTR_variant	1/3
POU5F1	NM_203289.6	c.-872A>G		5_prime_UTR_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POU5F1	ENST00000259915.13	c.406-767A>G		intron_variant		1	NM_002701.6	P1

Frequencies

GnomAD3 genomes AF: 0.0731 AC: 11121 AN: 152094 Hom.: 676 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0416

Gnomad ASJ AF: 0.0444

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.0427

Gnomad FIN AF: 0.0526

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0287

Gnomad OTH AF: 0.0746

GnomAD4 exome AF: 0.0343 AC: 35548 AN: 1034914 Hom.: 1082 Cov.: 31 AF XY: 0.0340 AC XY: 16666 AN XY: 489460

Gnomad4 AFR exome AF: 0.162

Gnomad4 AMR exome AF: 0.0366

Gnomad4 ASJ exome AF: 0.0487

Gnomad4 EAS exome AF: 0.177

Gnomad4 SAS exome AF: 0.0350

Gnomad4 FIN exome AF: 0.0590

Gnomad4 NFE exome AF: 0.0270

Gnomad4 OTH exome AF: 0.0506

GnomAD4 genome AF: 0.0731 AC: 11131 AN: 152212 Hom.: 678 Cov.: 32 AF XY: 0.0740 AC XY: 5508 AN XY: 74420

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.0415

Gnomad4 ASJ AF: 0.0444

Gnomad4 EAS AF: 0.167

Gnomad4 SAS AF: 0.0427

Gnomad4 FIN AF: 0.0526

Gnomad4 NFE AF: 0.0287

Gnomad4 OTH AF: 0.0753

Alfa AF: 0.0526 Hom.: 87

Bravo AF: 0.0784

Asia WGS AF: 0.115 AC: 400 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	5.3
Dann	Benign	0.76

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: rs11965454; hg19: chr6-31134591;