rs9468877

chr6-31175126-G-Achr6-31175126-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+5493C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,258 control chromosomes in the GnomAD database, including 1,997 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 0.16 (1997 hom., cov: 32)
• Consequence: POU5F1 ENST00000441888.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89

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:17203): (psoriasis susceptibility 1 candidate 3)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSORS1C3	NR_152835.1	n.293-1093C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POU5F1	ENST00000441888.7	c.-184+5493C>T		intron_variant		1
PSORS1C3	ENST00000412143.1	n.262-856C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23915 AN: 152140 Hom.: 1998 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.0872

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.157 AC: 23925 AN: 152258 Hom.: 1997 Cov.: 32 AF XY: 0.160 AC XY: 11947 AN XY: 74456

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.0876

Gnomad4 SAS AF: 0.242

Gnomad4 FIN AF: 0.210

Gnomad4 NFE AF: 0.152

Gnomad4 OTH AF: 0.156

Alfa AF: 0.151 Hom.: 2456

Bravo AF: 0.151

Asia WGS AF: 0.193 AC: 668 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	1.1
Dann	Benign	0.36

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9468877; hg19: chr6-31142903;