rs4713438

chr6-31179069-G-Achr6-31179069-G-Cchr6-31179069-G-T

Variant summary

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

The ENST00000441888.7(POU5F1):c.-184+1550C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 152,022 control chromosomes in the GnomAD database, including 4,405 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 0.23 (4405 hom., cov: 32)
• Consequence: POU5F1 ENST00000441888.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.461

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]

PSORS1C3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSORS1C3	NR_152835.1	n.293-5036C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POU5F1	ENST00000441888.7	c.-184+1550C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35251 AN: 151904 Hom.: 4394 Cov.: 32

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.0780

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.251

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

GnomAD4 genome AF: 0.232 AC: 35300 AN: 152022 Hom.: 4405 Cov.: 32 AF XY: 0.234 AC XY: 17377 AN XY: 74300

Gnomad4 AFR AF: 0.317

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.216

Gnomad4 EAS AF: 0.157

Gnomad4 SAS AF: 0.291

Gnomad4 FIN AF: 0.195

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.248

Alfa AF: 0.194 Hom.: 5293

Bravo AF: 0.237

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	3.0
Dann	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4713438; hg19: chr6-31146846;