6-31178062-T-C

Position:

• chr6-31178062-T-C

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSORS1C3	NR_152835.1	n.293-4029A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POU5F1	ENST00000441888.7	c.-184+2557A>G		intron_variant		1

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

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.450

Gnomad4 ASJ AF: 0.425

Gnomad4 EAS AF: 0.485

Gnomad4 SAS AF: 0.407

Gnomad4 FIN AF: 0.461

Gnomad4 NFE AF: 0.382

Gnomad4 OTH AF: 0.380

Alfa AF: 0.386 Hom.: 11692

Bravo AF: 0.385

Asia WGS AF: 0.449 AC: 1558 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.61

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3868542; hg19: chr6-31145839;