ENST00000441888.7:c.-184+2476G>A

Variant names:

• chr6-31178143-C-T
• rs887464
• ENST00000441888.7:c.-184+2476G>A

Variant summary

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

The ENST00000441888.7(POU5F1):​c.-184+2476G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 152,036 control chromosomes in the GnomAD database, including 12,341 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 (12341 hom., cov: 32)
• Consequence: POU5F1 ENST00000441888.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420
• Publications: 43 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 (EAS) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSORS1C3	NR_026816.2	n.293-244G>A		intron_variant	Intron 1 of 3
PSORS1C3	NR_152828.1	n.293-244G>A		intron_variant	Intron 1 of 4
PSORS1C3	NR_152829.1	n.293-244G>A		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POU5F1	ENST00000441888.7	c.-184+2476G>A		intron_variant	Intron 1 of 4	1		ENSP00000389359.2
PSORS1C3	ENST00000412143.2	n.94-244G>A		intron_variant	Intron 1 of 3	1

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60613 AN: 151918 Hom.: 12342 Cov.: 32

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.369

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

GnomAD4 genome AF: 0.399 AC: 60628 AN: 152036 Hom.: 12341 Cov.: 32 AF XY: 0.398 AC XY: 29556 AN XY: 74294

African (AFR) AF: 0.327 AC: 13557 AN: 41490

American (AMR) AF: 0.432 AC: 6597 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 1321 AN: 3466

East Asian (EAS) AF: 0.437 AC: 2256 AN: 5164

South Asian (SAS) AF: 0.290 AC: 1398 AN: 4814

European-Finnish (FIN) AF: 0.444 AC: 4684 AN: 10544

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.436 AC: 29664 AN: 67960

Other (OTH) AF: 0.371 AC: 784 AN: 2112

Alfa AF: 0.425 Hom.: 57569

Bravo AF: 0.396

Asia WGS AF: 0.380 AC: 1319 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	2.2
DANN	Benign	0.47
PhyloP100		-0.042
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: rs887464; hg19: chr6-31145920;