6-31175126-G-A

Variant names:

• chr6-31175126-G-A
• rs9468877
• ENST00000441888.7:c.-184+5493C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 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]

PSORS1C3 (HGNC:17203): (psoriasis susceptibility 1 candidate 3)

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 (SAS) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSORS1C3	NR_026816.2	n.554-856C>T		intron_variant	Intron 2 of 3
PSORS1C3	NR_152828.1	n.554-300C>T		intron_variant	Intron 2 of 4
PSORS1C3	NR_152829.1	n.820+563C>T		intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POU5F1	ENST00000441888.7	c.-184+5493C>T		intron_variant	Intron 1 of 4	1		ENSP00000389359.2
PSORS1C3	ENST00000412143.2	n.355-856C>T		intron_variant	Intron 2 of 3	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

African (AFR) AF: 0.156 AC: 6485 AN: 41550

American (AMR) AF: 0.150 AC: 2292 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 519 AN: 3466

East Asian (EAS) AF: 0.0876 AC: 454 AN: 5180

South Asian (SAS) AF: 0.242 AC: 1167 AN: 4826

European-Finnish (FIN) AF: 0.210 AC: 2231 AN: 10608

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10325 AN: 68006

Other (OTH) AF: 0.156 AC: 329 AN: 2110

Alfa AF: 0.152 Hom.: 4627

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
PhyloP100		-1.9
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: rs9468877; hg19: chr6-31142903;