rs9263800

Variant names:

• chr6-31166822-G-A
• rs9263800
• ENST00000606567.6:c.-394C>T

Variant summary

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

The ENST00000606567.6(POU5F1):​c.-394C>T 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 0.154 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_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.392
• Publications: 19 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=-0.94).
• 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 rank	MANE	Protein	UniProt
POU5F1	NM_002701.6	c.406-775C>T		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.406-775C>T		intron_variant	Intron 1 of 4	1	NM_002701.6	ENSP00000259915.7

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

African (AFR) AF: 0.157 AC: 3595 AN: 22866

American (AMR) AF: 0.110 AC: 1123 AN: 10184

Ashkenazi Jewish (ASJ) AF: 0.0914 AC: 1276 AN: 13954

East Asian (EAS) AF: 0.0445 AC: 905 AN: 20316

South Asian (SAS) AF: 0.0730 AC: 3691 AN: 50566

European-Finnish (FIN) AF: 0.107 AC: 803 AN: 7496

Middle Eastern (MID) AF: 0.147 AC: 394 AN: 2682

European-Non Finnish (NFE) AF: 0.165 AC: 149145 AN: 904866

Other (OTH) AF: 0.145 AC: 6074 AN: 41878

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

African (AFR) AF: 0.160 AC: 6628 AN: 41470

American (AMR) AF: 0.133 AC: 2028 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0922 AC: 320 AN: 3472

East Asian (EAS) AF: 0.0724 AC: 374 AN: 5168

South Asian (SAS) AF: 0.0683 AC: 329 AN: 4814

European-Finnish (FIN) AF: 0.115 AC: 1218 AN: 10588

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.159 AC: 10790 AN: 67998

Other (OTH) AF: 0.160 AC: 336 AN: 2104

Alfa AF: 0.149 Hom.: 4451

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
PhyloP100		-0.39
PromoterAI		-0.0097	Neutral
Mutation Taster		=300/0	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: rs9263800; hg19: chr6-31134599;