chr6-31174981-T-C

Variant names:

• chr6-31174981-T-C
• rs3132514
• ENST00000441888.7:c.-184+5638A>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+5638A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 152,248 control chromosomes in the GnomAD database, including 1,549 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 0.13 (1549 hom., cov: 32)
• Consequence: POU5F1 ENST00000441888.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0700
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSORS1C3	NR_026816.2	n.554-711A>G		intron_variant	Intron 2 of 3
PSORS1C3	NR_152828.1	n.554-155A>G		intron_variant	Intron 2 of 4
PSORS1C3	NR_152829.1	n.821-425A>G		intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POU5F1	ENST00000441888.7	c.-184+5638A>G		intron_variant	Intron 1 of 4	1		ENSP00000389359.2
PSORS1C3	ENST00000412143.2	n.355-711A>G		intron_variant	Intron 2 of 3	1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20205 AN: 152130 Hom.: 1546 Cov.: 32

Gnomad AFR AF: 0.0944

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.0798

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.0195

Gnomad SAS AF: 0.0935

Gnomad FIN AF: 0.0948

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.133 AC: 20209 AN: 152248 Hom.: 1549 Cov.: 32 AF XY: 0.127 AC XY: 9436 AN XY: 74452

African (AFR) AF: 0.0946 AC: 3930 AN: 41548

American (AMR) AF: 0.0796 AC: 1217 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 419 AN: 3468

East Asian (EAS) AF: 0.0195 AC: 101 AN: 5170

South Asian (SAS) AF: 0.0927 AC: 447 AN: 4822

European-Finnish (FIN) AF: 0.0948 AC: 1007 AN: 10620

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12512 AN: 68000

Other (OTH) AF: 0.114 AC: 241 AN: 2116

Alfa AF: 0.163 Hom.: 490

Bravo AF: 0.129

Asia WGS AF: 0.0600 AC: 212 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.6
DANN	Benign	0.68
PhyloP100		-0.070
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: rs3132514; hg19: chr6-31142758;