rs1108746

Variant names:

• chr6-31171727-C-A
• rs1108746
• ENST00000441888.7:c.-183-5680G>T

Variant summary

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

The ENST00000441888.7(POU5F1):​c.-183-5680G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 151,920 control chromosomes in the GnomAD database, including 1,570 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 0.14 (1570 hom., cov: 31)
• Consequence: POU5F1 ENST00000441888.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.899
• Publications: 12 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.184 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.-183-5680G>T		intron_variant	Intron 1 of 4	1		ENSP00000389359.2

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20795 AN: 151802 Hom.: 1567 Cov.: 31

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.0819

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.137 AC: 20823 AN: 151920 Hom.: 1570 Cov.: 31 AF XY: 0.143 AC XY: 10587 AN XY: 74222

African (AFR) AF: 0.106 AC: 4388 AN: 41452

American (AMR) AF: 0.160 AC: 2444 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 756 AN: 3468

East Asian (EAS) AF: 0.0821 AC: 422 AN: 5140

South Asian (SAS) AF: 0.194 AC: 935 AN: 4818

European-Finnish (FIN) AF: 0.232 AC: 2450 AN: 10540

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.130 AC: 8842 AN: 67934

Other (OTH) AF: 0.160 AC: 337 AN: 2112

Alfa AF: 0.134 Hom.: 857

Bravo AF: 0.131

Asia WGS AF: 0.110 AC: 382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.69
DANN	Benign	0.79
PhyloP100		-0.90
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: rs1108746; hg19: chr6-31139504;