6-31172231-C-T

Variant names:

• chr6-31172231-C-T
• rs3132520
• ENST00000441888.7:c.-183-6184G>A

Variant summary

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

The ENST00000441888.7(POU5F1):​c.-183-6184G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 151,860 control chromosomes in the GnomAD database, including 17,430 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 0.48 (17430 hom., cov: 31)
• Consequence: POU5F1 ENST00000441888.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0170
• Publications: 4 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POU5F1	ENST00000441888.7	c.-183-6184G>A		intron_variant	Intron 1 of 4	1		ENSP00000389359.2

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72608 AN: 151742 Hom.: 17419 Cov.: 31

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.464

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

GnomAD4 genome AF: 0.478 AC: 72641 AN: 151860 Hom.: 17430 Cov.: 31 AF XY: 0.477 AC XY: 35376 AN XY: 74202

African (AFR) AF: 0.456 AC: 18892 AN: 41418

American (AMR) AF: 0.522 AC: 7976 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1318 AN: 3470

East Asian (EAS) AF: 0.422 AC: 2168 AN: 5140

South Asian (SAS) AF: 0.435 AC: 2095 AN: 4818

European-Finnish (FIN) AF: 0.513 AC: 5406 AN: 10528

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.488 AC: 33141 AN: 67910

Other (OTH) AF: 0.464 AC: 975 AN: 2100

Alfa AF: 0.468 Hom.: 12861

Bravo AF: 0.479

Asia WGS AF: 0.446 AC: 1551 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	10
DANN	Benign	0.91
PhyloP100		0.017
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: rs3132520; hg19: chr6-31140008;