6-31175734-G-A

Variant names:

• chr6-31175734-G-A
• rs887466
• ENST00000441888.7:c.-184+4885C>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+4885C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 151,850 control chromosomes in the GnomAD database, including 12,506 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 0.40 (12506 hom., cov: 31)
• Consequence: POU5F1 ENST00000441888.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.502
• Publications: 40 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSORS1C3	NR_152829.1	n.775C>T		non_coding_transcript_exon_variant	Exon 3 of 5
PSORS1C3	NR_152834.1	n.775C>T		non_coding_transcript_exon_variant	Exon 3 of 7
PSORS1C3	NR_152838.1	n.775C>T		non_coding_transcript_exon_variant	Exon 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POU5F1	ENST00000441888.7	c.-184+4885C>T		intron_variant	Intron 1 of 4	1		ENSP00000389359.2
PSORS1C3	ENST00000412143.2	n.355-1464C>T		intron_variant	Intron 2 of 3	1

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61349 AN: 151732 Hom.: 12507 Cov.: 31

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.404 AC: 61371 AN: 151850 Hom.: 12506 Cov.: 31 AF XY: 0.410 AC XY: 30433 AN XY: 74188

African (AFR) AF: 0.367 AC: 15196 AN: 41408

American (AMR) AF: 0.471 AC: 7188 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 1545 AN: 3472

East Asian (EAS) AF: 0.486 AC: 2488 AN: 5122

South Asian (SAS) AF: 0.411 AC: 1977 AN: 4812

European-Finnish (FIN) AF: 0.463 AC: 4883 AN: 10544

Middle Eastern (MID) AF: 0.408 AC: 119 AN: 292

European-Non Finnish (NFE) AF: 0.397 AC: 26985 AN: 67918

Other (OTH) AF: 0.391 AC: 824 AN: 2106

Alfa AF: 0.404 Hom.: 48109

Bravo AF: 0.402

Asia WGS AF: 0.454 AC: 1575 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.4
DANN	Benign	0.67
PhyloP100		0.50
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: rs887466; hg19: chr6-31143511;