rs17190839

Variant names:

• chr6-31170930-G-A
• rs17190839
• ENST00000441888.7:c.-183-4883C>T

Variant summary

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

The ENST00000441888.7(POU5F1):​c.-183-4883C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0724 in 152,132 control chromosomes in the GnomAD database, including 658 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 0.072 (658 hom., cov: 32)
• Consequence: POU5F1 ENST00000441888.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.775
• Publications: 1 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POU5F1	NM_002701.6	c.-310C>T		upstream_gene_variant		ENST00000259915.13	NP_002692.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POU5F1	ENST00000441888.7	c.-183-4883C>T		intron_variant	Intron 1 of 4	1		ENSP00000389359.2
POU5F1	ENST00000259915.13	c.-310C>T		upstream_gene_variant		1	NM_002701.6	ENSP00000259915.7

Frequencies

GnomAD3 genomes AF: 0.0724 AC: 11009 AN: 152014 Hom.: 657 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0414

Gnomad ASJ AF: 0.0444

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.0383

Gnomad FIN AF: 0.0528

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0287

Gnomad OTH AF: 0.0722

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0724 AC: 11017 AN: 152132 Hom.: 658 Cov.: 32 AF XY: 0.0731 AC XY: 5439 AN XY: 74384

African (AFR) AF: 0.158 AC: 6547 AN: 41476

American (AMR) AF: 0.0413 AC: 632 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0444 AC: 154 AN: 3470

East Asian (EAS) AF: 0.154 AC: 799 AN: 5182

South Asian (SAS) AF: 0.0384 AC: 185 AN: 4822

European-Finnish (FIN) AF: 0.0528 AC: 559 AN: 10582

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0287 AC: 1953 AN: 67992

Other (OTH) AF: 0.0720 AC: 152 AN: 2112

Alfa AF: 0.0554 Hom.: 50

Bravo AF: 0.0780

Asia WGS AF: 0.0930 AC: 323 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.6
DANN	Benign	0.64
PhyloP100		-0.78
PromoterAI		0.013	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17190839; hg19: chr6-31138707;