6-31175805-A-C

Variant names:

• chr6-31175805-A-C
• rs3131018
• ENST00000441888.7:c.-184+4814T>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+4814T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.653 in 151,494 control chromosomes in the GnomAD database, including 32,390 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 0.65 (32390 hom., cov: 28)
• Consequence: POU5F1 ENST00000441888.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.226
• Publications: 57 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 (SAS) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSORS1C3	NR_152829.1	n.704T>G		non_coding_transcript_exon_variant	Exon 3 of 5
PSORS1C3	NR_152834.1	n.704T>G		non_coding_transcript_exon_variant	Exon 3 of 7
PSORS1C3	NR_152838.1	n.704T>G		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+4814T>G		intron_variant	Intron 1 of 4	1		ENSP00000389359.2
PSORS1C3	ENST00000412143.2	n.355-1535T>G		intron_variant	Intron 2 of 3	1

Frequencies

GnomAD3 genomes AF: 0.653 AC: 98799 AN: 151376 Hom.: 32379 Cov.: 28

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.720

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.712

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.641

Gnomad OTH AF: 0.642

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

GnomAD4 genome AF: 0.653 AC: 98850 AN: 151494 Hom.: 32390 Cov.: 28 AF XY: 0.653 AC XY: 48265 AN XY: 73966

African (AFR) AF: 0.665 AC: 27431 AN: 41240

American (AMR) AF: 0.649 AC: 9888 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.720 AC: 2491 AN: 3462

East Asian (EAS) AF: 0.709 AC: 3605 AN: 5086

South Asian (SAS) AF: 0.709 AC: 3408 AN: 4804

European-Finnish (FIN) AF: 0.615 AC: 6438 AN: 10474

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.641 AC: 43533 AN: 67890

Other (OTH) AF: 0.641 AC: 1352 AN: 2110

Alfa AF: 0.650 Hom.: 114782

Bravo AF: 0.654

Asia WGS AF: 0.681 AC: 2368 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	14
DANN	Benign	0.70
PhyloP100		0.23
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: rs3131018; hg19: chr6-31143582;