chr6-31178062-T-C

Variant names:

• chr6-31178062-T-C
• rs3868542
• ENST00000441888.7:c.-184+2557A>G

Variant summary

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

The ENST00000441888.7(POU5F1):​c.-184+2557A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 152,000 control chromosomes in the GnomAD database, including 11,606 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 0.39 (11606 hom., cov: 32)
• Consequence: POU5F1 ENST00000441888.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.515
• Publications: 30 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000441888.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSORS1C3	NR_026816.2		n.293-163A>G		intron	N/A
	PSORS1C3	NR_152828.1		n.293-163A>G		intron	N/A
	PSORS1C3	NR_152829.1		n.293-163A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU5F1	ENST00000441888.7	TSL:1	c.-184+2557A>G		intron	N/A	ENSP00000389359.2
	PSORS1C3	ENST00000412143.2	TSL:1	n.94-163A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58999 AN: 151882 Hom.: 11605 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.377

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

GnomAD4 genome AF: 0.388 AC: 59027 AN: 152000 Hom.: 11606 Cov.: 32 AF XY: 0.395 AC XY: 29359 AN XY: 74296

African (AFR) AF: 0.345 AC: 14318 AN: 41450

American (AMR) AF: 0.450 AC: 6874 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.425 AC: 1477 AN: 3472

East Asian (EAS) AF: 0.485 AC: 2505 AN: 5170

South Asian (SAS) AF: 0.407 AC: 1957 AN: 4814

European-Finnish (FIN) AF: 0.461 AC: 4867 AN: 10564

Middle Eastern (MID) AF: 0.403 AC: 117 AN: 290

European-Non Finnish (NFE) AF: 0.382 AC: 25945 AN: 67938

Other (OTH) AF: 0.380 AC: 801 AN: 2110

Alfa AF: 0.390 Hom.: 35946

Bravo AF: 0.385

Asia WGS AF: 0.449 AC: 1558 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.61
PhyloP100		-0.52
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: rs3868542; hg19: chr6-31145839;