6-31167111-T-C

Variant names:

• chr6-31167111-T-C
• rs3130931
• ENST00000513407.1:c.-1472A>G

Variant summary

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

The NM_203289.6(POU5F1):​c.-1169A>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 0.712 in 466,320 control chromosomes in the GnomAD database, including 119,397 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 0.74 (42280 hom., cov: 32)
  • Exomes 𝑓: 0.70 (77117 hom.)
• Consequence: POU5F1 NM_203289.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.491
• Publications: 60 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203289.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU5F1	NM_002701.6	MANE Select	c.406-1064A>G		intron	N/A	NP_002692.2
	POU5F1	NM_001173531.3		c.-683A>G		5_prime_UTR	Exon 1 of 5	NP_001167002.1	M1S623
	POU5F1	NM_203289.6		c.-1169A>G		5_prime_UTR	Exon 1 of 4	NP_976034.4	M1S623

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU5F1	ENST00000513407.1	TSL:1	c.-1472A>G		5_prime_UTR	Exon 1 of 3	ENSP00000475512.1	F2Z381
	POU5F1	ENST00000259915.13	TSL:1 MANE Select	c.406-1064A>G		intron	N/A	ENSP00000259915.7	Q01860-1
	POU5F1	ENST00000441888.7	TSL:1	c.-183-1064A>G		intron	N/A	ENSP00000389359.2	F2Z381

Frequencies

GnomAD3 genomes AF: 0.742 AC: 112782 AN: 152064 Hom.: 42241 Cov.: 32

Gnomad AFR AF: 0.837

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.774

Gnomad ASJ AF: 0.807

Gnomad EAS AF: 0.659

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.779

GnomAD4 exome AF: 0.697 AC: 218968 AN: 314138 Hom.: 77117 Cov.: 3 AF XY: 0.689 AC XY: 118538 AN XY: 171974

African (AFR) AF: 0.840 AC: 7771 AN: 9254

American (AMR) AF: 0.770 AC: 13305 AN: 17270

Ashkenazi Jewish (ASJ) AF: 0.803 AC: 10621 AN: 13220

East Asian (EAS) AF: 0.630 AC: 11038 AN: 17510

South Asian (SAS) AF: 0.614 AC: 29605 AN: 48218

European-Finnish (FIN) AF: 0.727 AC: 7762 AN: 10676

Middle Eastern (MID) AF: 0.773 AC: 2289 AN: 2960

European-Non Finnish (NFE) AF: 0.699 AC: 123755 AN: 177138

Other (OTH) AF: 0.717 AC: 12822 AN: 17892

GnomAD4 genome AF: 0.742 AC: 112876 AN: 152182 Hom.: 42280 Cov.: 32 AF XY: 0.740 AC XY: 55047 AN XY: 74380

African (AFR) AF: 0.837 AC: 34747 AN: 41520

American (AMR) AF: 0.773 AC: 11827 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.807 AC: 2801 AN: 3470

East Asian (EAS) AF: 0.660 AC: 3419 AN: 5182

South Asian (SAS) AF: 0.588 AC: 2836 AN: 4826

European-Finnish (FIN) AF: 0.729 AC: 7705 AN: 10572

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.692 AC: 47081 AN: 67996

Other (OTH) AF: 0.778 AC: 1644 AN: 2112

Alfa AF: 0.710 Hom.: 160044

Bravo AF: 0.754

Asia WGS AF: 0.702 AC: 2438 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.8
DANN	Benign	0.60
PhyloP100		0.49
PromoterAI		0.011	Neutral
Mutation Taster		=100/0	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: rs3130931; hg19: chr6-31134888;